Mammalian toxicity of herbicides used in intensive GM crop farming

Mesnage, Robin; Antoniou, Michael

doi:10.1016/b978-0-12-823674-1.00007-9

Cited by 8 publications

(3 citation statements)

References 147 publications

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“…These tumor-inducing effects of isoxaflutole are suggested to lay on the grounds of endocrine disruption [ 84 ]. Thyroid tumor induction was considered to occur via a possible disruption of the thyroid–pituitary hormonal feedback mechanisms [ 82 ], and since this proposed mode of thyroid tumor induction can apply to humans as well, a warning has recently been published that this mode of action of isoxaflutole is of public health relevance [ 85 ]. However, approval of the a.i.…”

Section: Discussionmentioning

confidence: 99%

Ecotoxicological Evaluation of Safener and Antimicrobial Additives in Isoxaflutole-Based Herbicide Formulations

Takács,

Lázár,

Siakwa

et al. 2024

Toxics

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The environmental load by isoxaflutole and its formulated herbicide products has increasingly become apparent because, after the ban of atrazine, isoxaflutole has become its replacement active ingredient (a.i.). Obtaining information regarding the fate of this a.i. in environmental matrices and its ecotoxicological effects on aquatic organisms is essential for the risk assessment of the herbicide. In this study, the effects of Merlin Flexx- and Merlin WG75 formulated isoxaflutole-based herbicide products and two selected additives (cyprosulfamide safener and 1,2-benzisothiazol-3(2H)-one antimicrobial agent) were investigated on Raphidocelis subcapitata in growth inhibition assays. In ecotoxicological tests, two conventional (optical density and chlorophyll-a content) and two induced fluorescence-based (Fv*/Fp: efficiency of the photosystem PSII and Rfd* changes in the observed ratio of fluorescence decrease) endpoints were determined by UV-spectrophotometer and by our FluoroMeter Module, respectively. Furthermore, dissipation of isoxaflutole alone and in its formulated products was examined by an HPLC-UV method. In ecotoxicological assays, the fluorescence-based Rfd* was observed as the most sensitive endpoint. In this study, the effects of the safener cyprosulfamide and the antimicrobial agent 1,2-benzisothiazol-3(2H)-one on R. subcapitata is firstly reported. The results indicated that the isoxaflutole-equivalent toxicity of the mixture of the isoxaflutole–safener–antimicrobial agent triggered lower toxicity (EC50 = 2.81 ± 0.22 mg/L) compared to the individual effect of the a.i. (EC50 = 0.02 ± 0.00 mg/L). The Merlin Flexx formulation (EC50 = 27.04 ± 1.41 mg/L) was found to be approximately 50-fold less toxic than Merlin WG75, which can be explained by the different chemical characteristics and quantity of additives in them. The additives influenced the dissipation of the a.i. in Z8 medium, as the DT50 value decreased by approximately 1.2- and 3.5-fold under light and dark conditions, respectively.

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Section: Discussionmentioning

confidence: 99%

Ecotoxicological Evaluation of Safener and Antimicrobial Additives in Isoxaflutole-Based Herbicide Formulations

Takács,

Lázár,

Siakwa

et al. 2024

Toxics

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“…An initial antiviral assay of the four studied chloroacetamide hits revealed toxicity in vitro that presents a challenge. , Chloroacetamide derivatives are most widely known for their use in herbicides, but they have recently demonstrated broad therapeutic potential including antimicrobial and anticancer properties. − As such, we caution against classifying our validated M pro inhibitors as potential leads at this stage. Rather, these compounds serve as proof of principle that AI-assisted workflows can be leveraged for the rapid discovery of targeted covalent ligands.…”

Section: Discussionmentioning

confidence: 99%

AI-Accelerated Design of Targeted Covalent Inhibitors for SARS-CoV-2

Joshi

Schultz

Wilson

et al. 2023

J. Chem. Inf. Model.

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Direct-acting antivirals for the treatment of the COVID-19 pandemic caused by the SARS-CoV-2 virus are needed to complement vaccination efforts. Given the ongoing emergence of new variants, automated experimentation, and active learning based fast workflows for antiviral lead discovery remain critical to our ability to address the pandemic’s evolution in a timely manner. While several such pipelines have been introduced to discover candidates with noncovalent interactions with the main protease (M pro ), here we developed a closed-loop artificial intelligence pipeline to design electrophilic warhead-based covalent candidates. This work introduces a deep learning-assisted automated computational workflow to introduce linkers and an electrophilic “warhead” to design covalent candidates and incorporates cutting-edge experimental techniques for validation. Using this process, promising candidates in the library were screened, and several potential hits were identified and tested experimentally using native mass spectrometry and fluorescence resonance energy transfer (FRET)-based screening assays. We identified four chloroacetamide-based covalent inhibitors of M pro with micromolar affinities (K I of 5.27 μM) using our pipeline. Experimentally resolved binding modes for each compound were determined using room-temperature X-ray crystallography, which is consistent with the predicted poses. The induced conformational changes based on molecular dynamics simulations further suggest that the dynamics may be an important factor to further improve selectivity, thereby effectively lowering K I and reducing toxicity. These results demonstrate the utility of our modular and data-driven approach for potent and selective covalent inhibitor discovery and provide a platform to apply it to other emerging targets.

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“…While numerous studies have highlighted the toxic impact of airborne pesticides on a range of organisms, including mammals, birds, fish, bees, and earthworms [165][166][167][168][169], it is important to note that these assessments provide a broad overview of potential toxic exposure rather than predicting a specific number of animal fatalities. For a more precise evaluation of risks, it becomes essential to combine field-specific, spatially referenced usage data with biodiversity monitoring, as suggested by Mesnage et al [170].…”

Section: Environmental Pollution From Airborne Pesticidesmentioning

confidence: 99%

Airborne Pesticides from Agricultural Practices: A Critical Review of Pathways, Influencing Factors, and Human Health Implications

Boonupara,

Udomkun,

Khan

et al. 2023

Toxics

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This critical review examines the release of pesticides from agricultural practices into the air, with a focus on volatilization, and the factors influencing their dispersion. The review delves into the effects of airborne pesticides on human health and their contribution to anthropogenic air pollution. It highlights the necessity of interdisciplinary research encompassing science, technology, public policy, and agricultural practices to effectively mitigate the risks associated with pesticide volatilization and spray dispersion. The text acknowledges the need for more research to understand the fate and transport of airborne pesticides, develop innovative application technologies, improve predictive modeling and risk assessment, and adopt sustainable pest management strategies. Robust policies and regulations, supported by education, training, research, and development, are crucial to ensuring the safe and sustainable use of pesticides for human health and the environment. By providing valuable insights, this review aids researchers and practitioners in devising effective and sustainable solutions for safeguarding human health and the environment from the hazards of airborne pesticides.

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Mammalian toxicity of herbicides used in intensive GM crop farming

Cited by 8 publications

References 147 publications

Ecotoxicological Evaluation of Safener and Antimicrobial Additives in Isoxaflutole-Based Herbicide Formulations

Ecotoxicological Evaluation of Safener and Antimicrobial Additives in Isoxaflutole-Based Herbicide Formulations

AI-Accelerated Design of Targeted Covalent Inhibitors for SARS-CoV-2

Airborne Pesticides from Agricultural Practices: A Critical Review of Pathways, Influencing Factors, and Human Health Implications

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