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Guerrero Schimpf et al., 2018

Guerrero Schimpf, M., Milesi, M. M., Luque, E. H., & Varayoud, J.m “Glyphosate-based herbicide enhances the uterine sensitivity to estradiol in rats,” Journal of Endocrinology, 2018, 239(2), 197-213. DOI: 10.1530/JOE-18-0207.

ABSTRACT:

In a previous work, we detected that postnatal exposure to a glyphosate-based herbicide (GBH) alters uterine development in prepubertal rats causing endometrial hyperplasia and increasing cell proliferation. Our goal was to determine whether exposure to low-dose of a GBH during postnatal development might enhance the sensitivity of the uterus to an estrogenic treatment. Female Wistar pups were subcutaneously injected with saline solution (control) or GBH using the reference dose (2 mg/kg/day, EPA) on postnatal days (PND) 1, 3, 5, and 7. At weaning (PND21), female rats were bilaterally ovariectomized and treated with silastic capsules containing 17beta-estradiol (E2, 1mg/ml) until they were two months of age. On PND60, uterine samples were removed and processed for histology, immunohistochemistry and mRNA extraction to evaluate: i) uterine morphology, ii) uterine cell proliferation by the detection of Ki67, iii) the expression of the estrogen receptors alpha (ESR1) and beta (ESR2), and iv) the expression of WNT7A and beta-catenin. GBH-exposed animals showed increased luminal epithelial height and stromal nuclei density. The luminal and glandular epithelium were markedly hyperplastic in 43% of GBH-exposed animals. GBH exposure caused an increase in E2-induced cell proliferation in association with an induction of both ESR1 and ESR2. GBH treatment decreased membranous and cytoplasmic expression of beta-catenin in luminal and glandular epithelial cells and increased WNT7A expression in the luminal epithelium. These results suggest that early postnatal exposure to a GBH enhances the sensitivity of the rat uterus to estradiol, and induces histomorphological and molecular changes associated with uterine hyperplasia. FULL TEXT

Green, 2018

Green, J. M., “The rise and future of glyphosate and glyphosate-resistant crops,” Pest Management Science, 2018, 74(5), 1035-1039. DOI: 10.1002/ps.4462.

ABSTRACT:

Glyphosate and glyphosate-resistant crops had a revolutionary impact on weed management practices, but the epidemic of glyphosate-resistant (GR) weeds is rapidly decreasing the value of these technologies. In areas that fully adopted glyphosate and GR crops, GR weeds evolved and glyphosate and glyphosate traits now must be combined with other technologies. The chemical company solution is to combine glyphosate with other chemicals, and the seed company solution is to combine glyphosate resistance with other traits. Unfortunately, companies have not discovered a new commercial herbicide mode-of-action for over 30 years and have already developed or are developing traits for all existing herbicide types with high utility. Glyphosate mixtures and glyphosate trait combinations will be the mainstays of weed management for many growers, but are not going to be enough to keep up with the capacity of weeds to evolve resistance. Glufosinate, auxin, HPPD-inhibiting and other herbicide traits, even when combined with glyphosate resistance, are incremental and temporary solutions. Herbicide and seed businesses are not going to be able to support what critics call the chemical and transgenic treadmills for much longer. The long time without the discovery of a new herbicide mode-of-action and the epidemic of resistant weeds is forcing many growers to spend much more to manage weeds and creating a worst of times, best of times predicament for the crop protection and seed industry. (c) 2016 Society of Chemical Industry.  FULL TEXT

Gillezeau et al., 2019

Gillezeau, Christina, van Gerwen, Maaike, Shaffer, Rachel M, Rana, Iemaan, Zhang, Luoping, Sheppard, Lianne, & Taioli, Emanuela, “The evidence of human exposure to glyphosate: a review,” Environmental Health, 2019, 18(1), 2. DOI: 10.1186/s12940-018-0435-5.

ABSTRACT:

BACKGROUND: Despite the growing and widespread use of glyphosate, a broad-spectrum herbicide and desiccant, very few studies have evaluated the extent and amount of human exposure.

OBJECTIVE: We review documented levels of human exposure among workers in occupational settings and the general population.

METHODS: We conducted a review of scientific publications on glyphosate levels in humans; 19 studies were identified, of which five investigated occupational exposure to glyphosate, 11 documented the exposure in general populations, and three reported on both.

RESULTS: Eight studies reported urinary levels in 423 occupationally and para-occupationally exposed subjects; 14 studies reported glyphosate levels in various biofluids on 3298 subjects from the general population. Average urinary levels in occupationally exposed subjects varied from 0.26 to 73.5 mug/L; environmental exposure urinary levels ranged from 0.16 to 7.6 mug/L. Only two studies measured temporal trends in exposure, both of which show increasing proportions of individuals with detectable levels of glyphosate in their urine over time.

CONCLUSIONS: The current review highlights the paucity of data on glyphosate levels among individuals exposed occupationally, para-occupationally, or environmentally to the herbicide. As such, it is challenging to fully understand the extent of exposure overall and in vulnerable populations such as children. We recommend further work to evaluate exposure across populations and geographic regions, apportion the exposure sources (e.g., occupational, household use, food residues), and understand temporal trends. FULL TEXT

Feat-Vetel et al., 2018

Feat-Vetel, Justyne, Larrigaldie, Vanessa, Meyer-Dilhet, Geraldine, Herzine, Ameziane, Mougin, Camille, Laugeray, Anthony, Gefflaut, Thierry, Richard, Olivier, Quesniaux, Valerie, Montecot-Dubourg, Celine, & Mortaud, Stephane, “Multiple effects of the herbicide glufosinate-ammonium and its main metabolite on neural stem cells from the subventricular zone of newborn mice,” NeuroToxicology, 2018, 69, 152-163. DOI: 10.1016/j.neuro.2018.10.001.

ABSTRACT:

The globally used herbicide glufosinate-ammonium (GLA) is structurally analogous to the excitatory neurotransmitter glutamate, and is known to interfere with cellular mechanisms involved in the glutamatergic system. In this report, we used an in vitro model of murine primary neural stem cell culture to investigate the neurotoxicity of GLA and its main metabolite, 4-methylphosphinico-2-oxobutanoic acid (PPO). We demonstrated that GLA and PPO disturb ependymal wall integrity in the ventricular-subventricular zone (V-SVZ) and alter the neuro-glial differentiation of neural stem cells. GLA and PPO impaired the formation of cilia, with reduced Celsr2 expression after PPO exposure. GLA promoted the differentiation of neuronal and oligodendroglial cells while PPO increased B1 cell population and impaired neuronal fate of neural stem cells. These results confirm our previous in vivo report that developmental exposure to GLA alters neurogenesis in the SVZ, and neuroblast migration along the rostral migratory stream. They also highlight the importance of investigating the toxicity of pesticide degradation products. Indeed, not only GLA, but also its metabolite PPO disrupts V-SVZ homeostasis and provides a novel cellular mechanism underlying GLA-induced neurodevelopmental toxicity. Furthermore, we were able to demonstrate a neurotoxic activity of a metabolite of GLA different from that of GLA active substance for the very first time. FULL TEXT

EPA, 2018

Environmental Protection Agency, “Occupational Pesticide Handler Unit Exposure Surrogate Reference Table,” Office of Pesticide Programs, 2018, Available at: https://www.epa.gov/pesticide-science-and-assessing-pesticide-risks/exposure-surrogate-reference-table-pesticide-risk.

SUMMARY:

The Exposure Surrogate Reference Table provides pesticide exposure information for risk assessment based on exposure scenarios, exposure routes and applicable personal protective equipment. FULL TEXT

DeVito, 2017

DeVito, Michael, “Update on NTP Studies of Glyphosate,” Presented at the National Toxicology Program (NTP) Board of Scientific Counselors Meeting, December 7-8, 2017.

SUMMARY:

Not available.  FULL TEXT

Dellaferrera et al., 2018

Dellaferrera, Ignacio, Cortés, Eduardo, Panigo, Elisa, De Prado, Rafael, Christoffoleti, Pedro, & Perreta, Mariel, “First Report of Amaranthus hybridus with Multiple Resistance to 2,4-D, Dicamba, and Glyphosate,” Agronomy, 2018, 8(8). DOI: 10.3390/agronomy8080140.

ABSTRACT:

In many countries, Amaranthus hybridus is a widespread weed in agricultural systems. The high prolificacy and invasive capacity as well as the resistance of some biotypes to herbicides are among the complications of handling this weed. This paper reports on the first A. hybridus biotypes with resistance to auxinic herbicides and multiple resistance to auxinic herbicides and the EPSPs inhibitor, glyphosate. Several dose response assays were carried out to determine and compare sensitivity of six population of A. hybridus to glyphosate, 2,4-D, and dicamba. In addition, shikimic acid accumulation and piperonil butoxide effects on 2,4-D and dicamba metabolism were tested in the same populations. The results showed four populations were resistant to dicamba and three of these were also resistant to 2,4-D, while only one population was resistant to glyphosate. The glyphosate-resistant population also showed multiple resistance to auxinic herbicides. Pretreatment with piperonil butoxide (PBO) followed by 2,4-D or dicamba resulted in the death of all individual weeds independent of herbicide or population. FULL TEXT

Defarge et al., 2018

Defarge, N., Spiroux de Vendomois, J., & Seralini, G. E., “Toxicity of formulants and heavy metals in glyphosate-based herbicides and other pesticides,”  Toxicology Reports, 2018, 5, 156-163. DOI: 10.1016/j.toxrep.2017.12.025.

ABSTRACT:

The major pesticides of the world are glyphosate-based herbicides (GBH), and their toxicity is highly debated. To understand their mode of action, the comparative herbicidal and toxicological effects of glyphosate (G) alone and 14 of its formulations were studied in this work, as a model for pesticides. GBH are mixtures of water, with commonly 36-48% G claimed as the active principle. As with other pesticides, 10-20% of GBH consist of chemical formulants. We previously identified these by mass spectrometry and found them to be mainly families of petroleum-based oxidized molecules, such as POEA, and other contaminants. We exposed plants and human cells to the components of formulations, both mixed and separately, and measured toxicity and human cellular endocrine disruption below the direct toxicity experimentally measured threshold. G was only slightly toxic on plants at the recommended dilutions in agriculture, in contrast with the general belief. In the short term, the strong herbicidal and toxic properties of its formulations were exerted by the POEA formulant family alone. The toxic effects and endocrine disrupting properties of the formulations were mostly due to the formulants and not to G. In this work, we also identified by mass spectrometry the heavy metals arsenic, chromium, cobalt, lead and nickel, which are known to be toxic and endocrine disruptors, as contaminants in 22 pesticides, including 11 G-based ones. This could also explain some of the adverse effects of the pesticides. In in vivo chronic regulatory experiments that are used to establish the acceptable daily intakes of pesticides, G or other declared active ingredients in pesticides are assessed alone, without the formulants. Considering these new data, this assessment method appears insufficient to ensure safety. These results, taken together, shed a new light on the toxicity of these major herbicides and of pesticides in general. FULL TEXT

de Souza et al., 2017

de Souza, Janaina Sena, Kizys, Marina Malta Letro, da Conceicao, Rodrigo Rodrigues, Glebocki, Gabriel, Romano, Renata Marino, Ortiga-Carvalho, Tania Maria, Giannocco, Gisele, da Silva, Ismael Dale Cotrim Guerreiro, Dias da Silva, Magnus Regios, Romano, Marco Aurelio, & Chiamolera, Maria Izabel, “Perinatal exposure to glyphosate-based herbicide alters the thyrotrophic axis and causes thyroid hormone homeostasis imbalance in male rats,” Toxicology, 2017, 377, 25-37. DOI: 10.1016/j.tox.2016.11.005.

ABSTRACT:

Glyphosate-based herbicides (GBHs) are widely used in agriculture. Recently, several animal and epidemiological studies have been conducted to understand the effects of these chemicals as an endocrine disruptor for the gonadal system. The aim of the present study was to determine whether GBHs could also disrupt the hypothalamic-pituitary-thyroid (HPT) axis. Female pregnant Wistar rats were exposed to a solution containing GBH Roundup((R))Transorb (Monsanto). The animals were divided into three groups (control, 5mg/kg/day or 50mg/kg/day) and exposed from gestation day 18 (GD18) to post-natal day 5 (PND5). Male offspring were euthanized at PND 90, and blood and tissues samples from the hypothalamus, pituitary, liver and heart were collected for hormonal evaluation (TSH-Thyroid stimulating hormone, T3-triiodothyronine and T4-thyroxine), metabolomic and mRNA analyses of genes related to thyroid hormone metabolism and function. The hormonal profiles showed decreased concentrations of TSH in the exposed groups, with no variation in the levels of the thyroid hormones (THs) T3 and T4 between the groups. Hypothalamus gene expression analysis of the exposed groups revealed a reduction in the expression of genes encoding deiodinases 2 (Dio2) and 3 (Dio3) and TH transporters Slco1c1 (former Oatp1c1) and Slc16a2 (former Mct8). In the pituitary, Dio2, thyroid hormone receptor genes (Thra1 and Thrb1), and Slc16a2 showed higher expression levels in the exposed groups than in the control group. Interestingly, Tshb gene expression did not show any difference in expression profile between the control and exposed groups. Liver Thra1 and Thrb1 showed increased mRNA expression in both GBH-exposed groups, and in the heart, Dio2, Mb, Myh6 (former Mhca) and Slc2a4 (former Glut4) showed higher mRNA expression in the exposed groups. Additionally, correlation analysis between gene expression and metabolomic data showed similar alterations as detected in hypothyroid rats. Perinatal exposure to GBH in male rats modified the HPT set point, with lower levels of TSH likely reflecting post-translational events. Several genes regulated by TH or involved in TH metabolism and transport presented varying degrees of gene expression alteration that were probably programmed during intrauterine exposure to GBHs and reflects in peripheral metabolism. In conclusion, the role of GBH exposure in HPT axis disruption should be considered in populations exposed to this herbicide. FULL TEXT

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