Glyphosate Use, Toxicity and Occurrence in Food

Martins-Gomes

et al. 2022

Toxics

In this work, three pesticides of different physicochemical properties, namely, glyphosate (herbicide), imidacloprid (insecticide) and imazalil (fungicide), were selected to assess their cytotoxicity against distinct cell models (Caco-2, HepG2, A431, HaCaT, SK-MEL-5 and RAW 264.7 cells) to mimic gastrointestinal and skin exposure with potential systemic effect. Cells were subjected to different concentrations of selected pesticides for 24 h or 48 h. Cell viability was assessed by Alamar Blue assay, morphological changes by bright-field microscopy and the IC50 values were calculated. Cytotoxic profiles were analysed using the physico-chemical parameters of the pesticides, namely: molecular weight, water solubility, the partition coefficient in the n-octanol/water (Log Pow) system, the topological polar surface area (TPSA), and number of hydrogen-bonds (donor/acceptor) and rotatable bonds. Results showed that glyphosate did not reduce cell viability (up to 1 mM), imidacloprid induced moderate toxicity (IC50 > 1 mM for Caco-2 cells while IC50 = 305.9 ± 22.4 μM for RAW 264.7 cells) and imazalil was highly cytotoxic (IC50 > 253.5 ± 3.37 for Caco-2 cells while IC50 = 31.3 ± 2.7 μM for RAW 264.7 cells) after 24 h exposure. Toxicity was time-dependent as IC50 values at 48 h exposure were lower, and decrease in cell viability was accompanied by changes in cell morphology. Pesticides toxicity was found to be directly proportional with their Log Pow, indicating that the affinity to a lipophilic environment such as the cell membranes governs their toxicity. Toxicity is inverse to pesticides TPSA, but lower TPSA favours membrane permeation. The lower toxicity against Caco-2 cells was attributed to the physiology and metabolism of cell barriers equipped with various ABC transporters. In conclusion, physicochemical factors such as Log Pow, TPSA and H-bond are likely to be directly correlated with pesticide-induced toxicity, thus being key factors to potentially predict the toxicity of other compounds.

Section: Discussionmentioning

confidence: 99%

In Vitro Assessment of Pesticides Toxicity and Data Correlation with Pesticides Physicochemical Properties for Prediction of Toxicity in Gastrointestinal and Skin Contact Exposure

Martins-Gomes

et al. 2022

Toxics

“…Especially since it is applied intensively to agricultural lands, its residues can be found in water, soil, plants, food products and human urine. Glyphosate is classified in category 2a as a possible human carcinogen according to the International Agency for Research on Cancer (IARC) 5 , 6 . The herbicidal effect of glyphosate is based on the inhibition of the enzyme 5-enolypyruvilshikimate-3-phosphate synthase (EPSP), which is produced in plants, fungi and some microorganisms.…”

Section: Introductionmentioning

confidence: 99%

“…As a result, the organism cannot synthesize the aromatic amino acids it needs to survive and the organism dies. There is also information in the literature that glyphosate inhibits the acetyl-cholinesterase enzyme and induces oxidative stress 6 , 7 .…”

Section: Introductionmentioning

confidence: 99%

Spectroscopic contribution to glyphosate toxicity profile and the remedial effects of Momordica charantia

Yalçın

Çavuşoğlu

2022

Sci Rep

In this study, the glyphosate toxicity and the toxicity-reducing role of bitter melon extract (Bmex) (Momordica charantia L.) were investigated in Allium cepa L. test material. The toxicity of glyphosate and protective role of Bmex were investigated with the help of physiological (germination, root elongation and weight gain), cytogenetic (mitotic index-MI, micronucleus-MN and chromosomal abnormalities-CAs), biochemical (malondialdehyde-MDA, superoxide dismutase-SOD and catalase-CAT) and anatomical (root meristem cell damage) parameters. The genotoxicity mechanism of glyphosate was elucidated by spectral analysis. A. cepa bulbs were divided into six groups as one control and five applications. Tap water was applied to the bulbs in the control group for 72 h. Glyphosate (500 mg/L) and two different doses of Bmex (350 and 700 mg/L) were applied to the bulbs in the treatment group for 72 h. At the end of the period, the germinated bulbs were prepared for experimental analyses, measurements and observations by applying routine preparation procedures. As a result, glyphosate administration caused a significant (p < 0.05) decrease in all selected physiological parameter values, and significant (p < 0.05) increases in the number of cytogenetic parameters (except MI), the levels of biochemical parameters and the severity of anatomical damage. Glyphosate promoted CAs such as fragment, sticky chromosome, bridge and unequal distribution of chromatin in root tip meristem cells. By spectral analysis, it was determined that glyphosate interacts directly with DNA and causes genotoxicity. It also caused anatomical damages such as epidermis cell damage, cortex cell damage, flattened cell nucleus, binuclear cell and irregular vascular tissue in root tip meristem cells. Co-administration of glyphosate with Bmex at two different doses (350 and 700 mg/L) reduced the toxicity of glyphosate and led to significant (p < 0.05) improvements in the values of all parameters examined. It was determined that this improvement was even more pronounced at 700 mg/L dose of Bmex. As a result, it was determined that glyphosate herbicide caused multi-dimensional toxicity in A. cepa test material, and Bmex reduced the effects of this toxicity due to its antioxidant properties. Therefore, glyphosate dose ranges need to be reconsidered, especially considering non-target organisms in agricultural applications. In addition, antioxidant products such as Bmex should be included in the daily diet in order to reduce the toxic effects of environmental agents such as pesticides.

“…Here, we examined whether a model based on the nucleo-shuttling of the ATM protein is also relevant for the exposure to pesticide. To this aim, human skin fibroblast and brain astrocyte cells from different RIANS statuses were exposed to six current pesticides of domestic and environmental interest, namely gamma-hexachlorocyclohexane (lindane, HCH) [ 30 , 31 ], atrazine (ATR) [ 32 ], glyphosate (GBH) [ 33 ], permethrin (PER) [ 34 ], pentachlorophenol (PCP) [ 35 , 36 ], and thiabendazole (TBZ) [ 37 ] ( Table 1 ), and subjected to immunofluorescence, with the RIANS biomarkers as endpoints. The general objective of this paper is to better identify, document, and quantify the molecular steps of the individual response to pesticides that may lead to cellular death, whatever its form.…”

Section: Introductionmentioning

confidence: 99%

DNA Double-Strand Breaks Induced in Human Cells by 6 Current Pesticides: Intercomparisons and Influence of the ATM Protein

et al. 2022

A mechanistic model from radiobiology has emerged by pointing out that the radiation-induced nucleo-shuttling of the ATM protein (RIANS) initiates the recognition, the repair of DNA double-strand breaks (DSB), and the final response to genotoxic stress. More recently, we provided evidence in this journal that the RIANS model is also relevant for exposure to metal ions. To document the role of the ATM-dependent DSB repair and signaling after pesticide exposure, we applied six current pesticides of domestic and environmental interest (lindane, atrazine, glyphosate, permethrin, pentachlorophenol and thiabendazole) to human skin fibroblast and brain cells. Our findings suggest that each pesticide tested may induce DSB at a rate that depends on the pesticide concentration and the RIANS status of cells. At specific concentration ranges, the nucleo-shuttling of ATM can be delayed, which impairs DSB recognition and repair, and contributes to toxicity. Interestingly, the combination of copper sulfate and thiabendazole or glyphosate was found to have additive or supra-additive effects on DSB recognition and/or repair. A general mechanistic model of the biological response to metal and/or pesticide is proposed to define quantitative endpoints for toxicity.