Bibliography Tag: roundup

Mesnage et al., 2021C

Mesnage R, Mazzacuva F, Caldwell A, Halket J, Antoniou MN. “Urinary excretion of herbicide co-formulants after oral exposure to roundup MON 52276 in rats.” Environmental Research. 2021 Jun;197:111103. DOI: 10.1016/j.envres.2021.111103.


The toxicity of surfactants, which are an integral component of glyphosate-formulated products is an underexplored and highly debated subject. Since biomonitoring human exposure to glyphosate co-formulants is considered as a public health priority, we developed and validated a high-resolution mass spectrometry method to measure the urinary excretion of surfactants present in Roundup MON 52276, the European Union (EU) representative formulation of glyphosate-based herbicides. Quantification was performed measuring the 5 most abundant compounds in the mixture. We validated the method and showed that it is highly accurate, precise and reproducible with a limit of detection of 0.0004 μg/mL. We used this method to estimate the oral absorption of MON 52276 surfactants in Sprague-Dawley rats exposed to three concentrations of MON 52276 via drinking water for 90 days. MON 52276 surfactants were readily detected in urine of rats administered with this commercial Roundup formulation starting from a low concentration corresponding to the EU glyphosate acceptable daily intake. Our results provide a first step towards the implementation of surfactant co-formulant biomonitoring in human populations. FULL TEXT

de Melo et al., 2019

de Melo, M. S., Nazari, E. M., Joaquim-Justo, C., Muller, Y. M. R., & Gismondi, E.; “Effects of low glyphosate-based herbicide concentrations on endocrine-related gene expression in the decapoda Macrobrachium potiuna;” Environmental Science and Pollution Research International, 2019, 26(21), 21535-21545; DOI: 10.1007/s11356-019-05496-1.


Glyphosate-based herbicides (GBH) are the most used herbicides worldwide and are considered as endocrine-disrupting compounds (EDC) for non-target organisms. However, effects of GBH on their endocrine systems remain poorly understood. Thus, the aim of this study was to assess the effects of low concentrations of Roundup WG(R) on growth and reproduction process molecules in both males and females of the decapod crustacean Macrobrachium potiuna, by the relative transcript expression levels of the ecdysteroid receptor (EcR), the molt-inhibiting hormone (MIH), and the vitellogenin (Vg) genes. Prawns were exposed to three concentrations of GBH (0.0065, 0.065, and 0.28 mg L(-1)) for 7 and 14 days. The results revealed that only in males the three genes transcript levels were influenced by the GBH concentration, time of exposure, and the interaction between the concentrations and time of exposure, suggesting that males were more sensitive to GBH than females. For males, after 7 days of exposure at 0.065 mg L(-1), EcR and MIH were over-expressed, while the Vg expression was only over-expressed after 14 days. The present study highlighted that GBH impacted endocrine systems of M. potiuna. Moreover, EcR and MIH gene expressions could be promising EDC biomarkers of exposure in crustaceans. These results also indicate that GBH concentrations, considered secure by regulatory agencies, should be reviewed to minimize the effects on non-target organisms. FULL TEXT

Stur et al., 2019

Stur, E., Aristizabal-Pachon, A. F., Peronni, K. C., Agostini, L. P., Waigel, S., Chariker, J., Miller, D. M., Thomas, S. D., Rezzoug, F., Detogni, R. S., Reis, R. S. D., Silva Junior, W. A., & Louro, I. D.; “Glyphosate-based herbicides at low doses affect canonical pathways in estrogen positive and negative breast cancer cell lines;” Plos One, 2019, 14(7), e0219610; DOI: 10.1371/journal.pone.0219610.


Glyphosate is a broad-spectrum herbicide that is used worldwide. It represents a potential harm to surface water, and when commercially mixed with surfactants, its uptake is greatly magnified. The most well-known glyphosate-based product is Roundup. This herbicide is potentially an endocrine disruptor and many studies have shown the cytotoxicity potential of glyphosate-based herbicides. In breast cancer (BC) cell lines it has been demonstrated that glyphosate can induce cellular proliferation via estrogen receptors. Therefore, we aimed to identify gene expression changes in ER+ and ER- BC cell lines treated with Roundup and AMPA, to address changes in canonical pathways that would be related or not with the ER pathway, which we believe could interfere with cell proliferation. Using the Human Transcriptome Arrays 2.0, we identified gene expression changes in MCF-7 and MDA-MB-468 exposed to low concentrations and short exposure time to Roundup Original and AMPA. The results showed that at low concentration (0.05% Roundup) and short exposure (48h), both cell lines suffered deregulation of 11 canonical pathways, the most important being cell cycle and DNA damage repair pathways. Enrichment analysis showed similar results, except that MDA-MB-468 altered mainly metabolic processes. In contrast, 48h 10mM AMPA showed fewer differentially expressed genes, but also mainly related with metabolic processes. Our findings suggest that Roundup affects survival due to cell cycle deregulation and metabolism changes that may alter mitochondrial oxygen consumption, increase ROS levels, induce hypoxia, damage DNA repair, cause mutation accumulation and ultimately cell death. To our knowledge, this is the first study to analyze the effects of Roundup and AMPA on gene expression in triple negative BC cells. Therefore, we conclude that both compounds can cause cellular damage at low doses in a relatively short period of time in these two models, mainly affecting cell cycle and DNA repair. FULL TEXT

Slaby et al., 2019

Slaby, S., Titran, P., Marchand, G., Hanotel, J., Lescuyer, A., Lepretre, A., Bodart, J. F., Marin, M., & Lemiere, S., “Effects of glyphosate and a commercial formulation Roundup(R) exposures on maturation of Xenopus laevis oocytes,” Environmental Science and Pollution Research International, 2019. DOI: 10.1007/s11356-019-04596-2.


Pesticides are often found at high concentrations in small ponds near agricultural field where amphibians are used to live and reproduce. Even if there are many studies on the impacts of phytopharmaceutical active ingredients in amphibian toxicology, only a few are interested in the earlier steps of their life cycle. While their populations are highly threatened with extinction. The aim of this work is to characterize the effects of glyphosate and its commercial formulation Roundup(R) GT Max on the Xenopus laevis oocyte maturation which is an essential preparation for the laying and the fertilization. Glyphosate is an extensively used herbicide, not only known for its effectiveness but also for its indirect impacts on non-target organisms. Our results showed that exposures to both forms of glyphosate delayed this hormone-dependent process and were responsible for spontaneous maturation. Severe and particular morphogenesis abnormalities of the meiotic spindle were also observed. The MAPK pathway and the MPF did not seem to be affected by exposures. The xenopus oocyte is particularly affected by the exposures and appears as a relevant model for assessing the effects of environmental contamination. FULL TEXT

Wozniak et al., 2018

Wozniak, E., Sicinska, P., Michalowicz, J., Wozniak, K., Reszka, E., Huras, B., Zakrzewski, J., & Bukowska, B., “The mechanism of DNA damage induced by Roundup 360 PLUS, glyphosate and AMPA in human peripheral blood mononuclear cells – genotoxic risk assessement,” Food and Chemical Toxicology, 2018, 120, 510-522. DOI: 10.1016/j.fct.2018.07.035.


Glyphosate is the most heavily applied among pesticides in the world, and thus human exposure to this substance continues to increase. WHO changed classification of glyphosate to probably cancerogenic to humans, thus there is urgent need to assess in detail genotoxic mechanism of its action. We have assessed the effect of glyphosate, its formulation (Roundup 360 PLUS) and its main metabolite (aminomethylphosphonic acid, AMPA) in the concentration range from 1 to 1000muM on DNA damage in human peripheral blood mononuclear cells (PBMCs). The cells were incubated for 24h. The compounds studied and formulation induced DNA single and double strand-breaks and caused purines and pyrimidines oxidation. None of compounds examined was capable of creating adducts with DNA, while those substances increased ROS (including (*)OH) level in PBMCs. Roundup 360 PLUS caused damage to DNA even at 5muM, while glyphosate and particularly AMPA induced DNA lesions from the concentration of 250muM and 500muM, respectively. DNA damage induced by glyphosate and its derivatives increased in order: AMPA, glyphosate, Roundup 360 PLUS. We may conclude that observed changes were not associated with direct interaction of xenobiotics studied with DNA, but the most probably they occurred through ROS-mediated effects. FULL TEXT

Luo et al., 2017

Luo, Lei, Wang, Fei, Zhang, Yiyuan, Zeng, Ming, Zhong, Caigao, & Xiao, Fang, “In vitro cytotoxicity assessment of Roundup (glyphosate) in L-02 hepatocytes,” Journal of Environmental Science and Health, Part B, 2017, 52(6), 410-417. DOI: 10.1080/03601234.2017.1293449.


The goal of the present study was to elucidate the in vitro cytotoxicity of Roundup and to reveal the possible related mechanisms in L-02 hepatocytes. By detecting reactive oxygen species (ROS) production, glutathione (GSH)/superoxide dismutase (SOD) levels, mitochondrial permeability transition pore (PTP) open rate, apoptosis-inducing factor (AIF) release, intracellular Ca2+ concentration, and alanine aminotransferease (ALT)/aspartate aminotransferase (AST) leakage, we determined that Roundup induced anti-oxidant system inhibition, mitochondria damage, DNA damage, membrane integrity and permeability changes, and apoptosis in L-02 hepatocytes. By revealing the mechanistic insights of Roundup-induced cytotoxicity, our results are valuable for the design of preventive and therapeutic strategies for the occupational population exposed to Roundup and other pesticides.

Krimsky and Gillam, 2018

Krimsky, Sheldon, & Gillam, Carey, “Roundup litigation discovery documents: implications for public health and journal ethics,” Journal of Public Health Policy, 2018, 39(3), 318-326. DOI: 10.1057/s41271-018-0134-z.


This paper reviews the court-released discovery documents obtained from litigation against Monsanto over its herbicide Roundup and through Freedom of Information Act requests (requests to regulatory agencies and public universities in the United States). We sought evidence of corporate malfeasance and undisclosed conflicts of interest with respect to issues of scientific integrity. The findings include evidence of ghostwriting, interference in journal publication, and undue influence of a federal regulatory agency.

Jiang et al., 2018

Jiang, X., Zhang, N., Yin, L., Zhang, W. L., Han, F., Liu, W. B., Chen, H. Q., Cao, J., & Liu, J. Y., “A commercial Roundup(R) formulation induced male germ cell apoptosis by promoting the expression of XAF1 in adult mice.,” Toxicology Letters, 2018, 296, 163-172, DOI: 10.1016/j.toxlet.2018.06.1067.


Roundup(R) is extensively used for weed control worldwide. Residues of this compound may lead to side effects of the male reproductive system. However, the toxic effects and mechanisms of Roundup(R) of male germ cells remain unclear. We aimed to investigate the apoptosis-inducing effects of Roundup(R) on mouse male germ cells and explore the role of a novel tumor suppressor XAF1 (X-linked inhibitor of apoptosis-associated factor 1) involved in this process. We demonstrated that Roundup(R) can impair spermatogenesis, decrease sperm motility and concentration, and increase the sperm deformity rate in mice. In addition, excessive apoptosis of germ cells accompanied by the overexpression of XAF1 occurred after Roundup(R) exposure both in vitro and in vivo. Furthermore, the low expression of XIAP (X-linked inhibitor of apoptosis) induced by Roundup(R) was inversely correlated with XAF1. Moreover, the knockdown of XAF1 attenuated germ cell apoptosis, improved XIAP expression and inhibited the activation of its downstream target proteins, caspase-3 and PARP, after Roundup(R) exposure. Taken together, our data indicated that XAF1 plays an important role in Roundup(R)-induced male germ cell apoptosis. The present study suggested that Roundup(R) exposure has potential negative implications on male reproductive health in mammals.

Hong et al., 2018

Hong, Y., Yang, X., Huang, Y., Yan, G., & Cheng, Y., “Assessment of the oxidative and genotoxic effects of the glyphosate-based herbicide Roundup on the freshwater shrimp, Macrobrachium nipponensis,” Chemosphere, 2018, 210, 896-906. DOI: 10.1016/j.chemosphere.2018.07.069.


In the present study, an acute toxic test was performed to assess the oxidative stress and genotoxic effects of the herbicide on the freshwater shrimp Macrobrachium nipponensis. The results showed that the 48-h and 96-h LC50 values of Roundup to M. nipponensis were 57.684mg/L and 11.237mg/L, respectively. For further investigation, the shrimps were exposed to sublethal concentrations of 0.35, 0.70, 1.40, 2.80 and 5.60mg/L for 96h. A significant decrease in total haemocytes count (THC) was observed at concentration of 5.60mg/L throughout the experiment. The level of superoxide dismutase (SOD), catalase (CAT) and total antioxidant capacity (T-AOC) in all the treatments decreased in a dose- and time-dependent manner except for the concentration group of 0.35mg/L. The malondialdehyde (MDA), hydrogen peroxide (H2O2) and protein carbonyl in serum increased significantly at concentrations of 2.80mg/L and 5.60mg/L. A significant decrease in acetylcholinesterase (AChE) activity was observed at each concentration (P0.05). In addition, the micronucleus (MN) frequency of haemocytes significantly increased (P0.05) at concentrations of 1.40, 2.80 and 5.60mg/L, whereas the comet ratio and %DNA in the tails exhibited a clear time- and dose-dependent response during the exposure. The analysis of the integrated biomarker response (IBR) showed the induction of oxidative stress biomarkers and the inhibition of antioxidants, and this dose-dependent relation suggests the sensitivity and availability of all the biomarkers. These results revealed that Roundup had a prominent toxic effect on M. nipponensis based on the antioxidative response inhibition and genotoxicity.

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.


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