Adjuvant contributes Roundup's unexpected effects on A549 cells

Hao, Youwu; Zhang, Yang; Cheng, Jiagao; Xu, Wenping; Xu, Zhiping; Gao, Jufang; Tao, Liming

doi:10.1016/j.envres.2020.109306

Cited by 21 publications

(18 citation statements)

References 37 publications

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“…Guilherme et al, exposing fish blood cells with Roundup formulation and its constituents, found that the genotoxic effect separately induced by POEA and glyphosate was not strengthened when the two substances were used in combination, ruling out a synergistic interaction between the ingredients of Roundup ( 52 ). Hao et al demonstrated that POEA and Roundup exposure induce oxidative DNA lesions and other biochemical changes in human A549 cells, which were not detected in cells treated with glyphosate alone ( 14 ).…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, the composition of numerous GBHs is unknown, that makes it very difficult for scientists to assess the health risks of certain adjuvants or the combined effects of different ingredients in GBHs. Notwithstanding, more and more evidence has emerged that certain adjuvants, such as polyethoxylated tallow amines (POEAs), are more toxic than glyphosate alone ( 13 , 14 ), and/or increase the toxicity of the active substance by allowing it to penetrate plant, but also animal and human, cells more easily, increasing formulations' toxicity ( 15 , 16 ). As a result of this recognition, GBHs containing these adjuvants are progressively being phased out and replaced by a new generation of co-formulants on the European market, but not in the US.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Micronucleus Formation Induced by Glyphosate and Glyphosate-Based Herbicides in Human Peripheral White Blood Cells

Nagy

Tessema

Szász

et al. 2021

Front. Public Health

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Glyphosate is the most commonly used herbicide around the world, which led to its accumulation in the environment and consequent ubiquitous human exposure. Glyphosate is marketed in numerous glyphosate-based herbicide formulations (GBHs) that include co-formulants to enhance herbicidal effect of the active ingredient, but are declared as inert substances. However, these other ingredients can have biologic activity on their own and may interact with the glyphosate in synergistic toxicity. In this study, we focused to compare the cytogenetic effect of the active ingredient glyphosate and three marketed GBHs (Roundup Mega, Fozat 480, and Glyfos) by investigating cytotoxicity with fluorescent co-labeling and WST-1 cell viability assay as well as genotoxicity with cytokinesis block micronucleus assay in isolated human mononuclear white blood cells. Glyphosate had no notable cytotoxic activity over the tested concentration range (0–10,000 μM), whereas all the selected GBHs induced significant cell death from 1,000 μM regardless of metabolic activation (S9). Micronucleus (MN) formation induced by glyphosate and its formulations at sub-cytotoxic concentrations (0–100 μM) exhibited a diverse pattern. Glyphosate caused statistically significant increase of MN frequency at the highest concentration (100 μM) after 20-h exposure. Contrarily, Roundup Mega exerted a significant genotoxic effect at 100 μM both after 4- and 20-h exposures; moreover, Glyfos and Fozat 480 also resulted in a statistically significant increase of MN frequency from the concentration of 10 μM after 4-h and 20-h treatment, respectively. The presence of S9 had no effect on MN formation induced by either glyphosate or GBHs. The differences observed in the cytotoxic and genotoxic pattern between the active principle and formulations confirm the previous concept that the presence of co-formulants in the formulations or the interaction of them with the active ingredient is responsible for the increased toxicity of herbicide products, and draw attention to the fact that GBHs are still currently in use, the toxicity of which rivals that of POEA-containing formulations (e.g., Glyfos) already banned in Europe. Hence, it is advisable to subject them to further comprehensive toxicological screening to assess the true health risks of exposed individuals, and to reconsider their free availability to any users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Micronucleus Formation Induced by Glyphosate and Glyphosate-Based Herbicides in Human Peripheral White Blood Cells

Nagy

Tessema

Szász

et al. 2021

Front. Public Health

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“…GBHs have adverse effects, such as toxic effects on human blood and peripheral blood mononuclear cells (PBMCs) (1-100 µg/mL), increased permeability of the blood-brain barrier (100 µM), increased ROS levels in epithelial cells, and decreased cell viability of several cell lines, including HepG2 (a liver hepatocellular carcinoma cell line) and JEG3 (a human choriocarcinoma cell line). The authors also mentioned that deleterious effects of G were improved by formulants used in GBH formulations because G alone, at a low concentration, had less impact than in formulations with the same level of G [4,12]. Moreover, formulants alone are more toxic than G or GBHs [12].…”

Section: Introductionmentioning

confidence: 99%

“…The authors also mentioned that deleterious effects of G were improved by formulants used in GBH formulations because G alone, at a low concentration, had less impact than in formulations with the same level of G [4,12]. Moreover, formulants alone are more toxic than G or GBHs [12]. Indeed, studies on formulants such as POEA and formulation such as Roundup have shown their toxicity for the cells.…”

Section: Introductionmentioning

confidence: 99%

Review: Mechanisms of Glyphosate and Glyphosate-Based Herbicides Action in Female and Male Fertility in Humans and Animal Models

Serra

Estienne

Vasseur³

et al. 2021

Cells

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Glyphosate (G), also known as N-(phosphonomethyl)glycine is the declared active ingredient of glyphosate-based herbicides (GBHs) such as Roundup largely used in conventional agriculture. It is always used mixed with formulants. G acts in particular on the shikimate pathway, which exists in bacteria, for aromatic amino acids synthesis, but this pathway does not exist in vertebrates. In recent decades, researchers have shown by using various animal models that GBHs are endocrine disruptors that might alter reproductive functions. Our review describes the effects of exposure to G or GBHs on the hypothalamic–pituitary–gonadal (HPG) axis in males and females in terms of endocrine disruption, cell viability, and proliferation. Most of the main regulators of the reproductive axis (GPR54, GnRH, LH, FSH, estradiol, testosterone) are altered at all levels of the HPG axis (hypothalamus, pituitary, ovaries, testis, placenta, uterus) by exposure to GBHs which are considered more toxic than G alone due to the presence of formulants such as polyoxyethylene tallow amine (POEA).” In addition, we report intergenerational impacts of exposure to G or GBHs and, finally, we discuss different strategies to reduce the negative effects of GBHs on fertility.

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“…Therefore, these cellular results support our lung in ammatory ndings of mice experiment after exposure to a lower dose of glyphosate. Recent data show that isopropylamine salt of glyphosate did not contribute to apoptotic and genotoxic effects on A549 cells (33). Therefore, our results need to be interpreted with caution as they are based on pure glyphosate.…”

Section: Discussionmentioning

confidence: 61%

Lung Inflammation from Single and Repetitive Exposure to Glyphosate

Pandher

Kirychuk

Schneberger

et al. 2021

Preprint

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Background: Glyphosate is an active ingredient in herbicides used in agriculture worldwide. Exposure to glyphosate has been associated with respiratory dysfunctions in agricultural workers. However, the ability of glyphosate to induce inflammation in the lung is not well studied. Therefore, we evaluated lung inflammatory response to glyphosate at agricultural relevant dose for single and repetitive exposures. Methods: Male C57BL/6 mice were intranasally exposed to glyphosate (1 μg/40 μl) for 1-day or once daily for 5-days, and 10-days. After the exposure periods, mice were euthanized to collect the bronchoalveolar lavage (BAL) fluid and lung tissue. Results: Repetitive exposure to glyphosate for 5-days and 10-days showed an increase of neutrophils in BAL fluid and eosinophil peroxidase levels in lungs, a marker for eosinophils. Leukocyte infiltration in lungs was further confirmed through lung histology. Th2 cytokines including IL-5 and IL-13 were increased in BAL fluid after 10-days of glyphosate exposure whereas IL-4 was not increased. Lung sections from all glyphosate groups showed higher expression for ICAM-1, VCAM-1, and vWF adhesion molecules. TLR-4 and TLR-2 expression was increased in lungs after repetitive exposure to glyphosate. Conclusions: We conclude that repetitive exposure to glyphosate induces migration of neutrophils and eosinophils and release of Th2 cytokines. This study, for the first time, provides evidence for the role of ICAM-1, VCAM-1 and vWF in lungs of glyphosate-treated animals.

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Adjuvant contributes Roundup's unexpected effects on A549 cells

Cited by 21 publications

References 37 publications

Micronucleus Formation Induced by Glyphosate and Glyphosate-Based Herbicides in Human Peripheral White Blood Cells

Micronucleus Formation Induced by Glyphosate and Glyphosate-Based Herbicides in Human Peripheral White Blood Cells

Review: Mechanisms of Glyphosate and Glyphosate-Based Herbicides Action in Female and Male Fertility in Humans and Animal Models

Lung Inflammation from Single and Repetitive Exposure to Glyphosate

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