Pesticides in Formulations: Toxicological and Regulatory Assessments, New Developments

A special issue of Toxics (ISSN 2305-6304). This special issue belongs to the section "Novel Methods in Toxicology Research".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 28830

Special Issue Editor


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Guest Editor
Institute of Biology, University of Caen Normandy, Network on Risks, Quality and Sustainable Environment MRSH, Esplanade de la Paix, CEDEX 5, CS 14032 Caen, France
Interests: long-term xenobiotic toxicology; mechanisms; human diseases; mammalian

Special Issue Information

Dear Colleagues,

It appears to most of us that the long-term effects of pesticides in ecosystems need to be better understood and their use regulated. New discoveries regarding the compositions of fully marketed formulations with components other than the declared active ingredients are poorly studied and rarely taken into account when establishing admissible daily intakes, for instance. Comparisons of the effects of pesticides used in the environment versus those of the declared active ingredients alone are rarely studied; however, this is crucial to shed light on the real toxicity of pesticides.

The aim of this Special Issue is to explain new discoveries, particularly regarding the long-term toxicities of pesticides in whole ecosystems, and, importantly, how these are taken into consideration by health and regulatory agencies. The scope is to understand the new developments in the knowledge of full formulations, especially compared to the known effects of the declared active ingredients alone. The understanding of the nature and toxicities of formulants other than the declared active ingredients will be of interest. The major pesticides of the world, i.e., glyphosate-based herbicides, which are being debated in all continents, will be focused on.

Any knowledge in various sciences helping to understand this topic is welcome; even reviews and technical, biological, epidemiological, sociological, theoretical, historical or multidisciplinary approaches are encouraged. How was the regulation of pesticides established and how has it evolved? How quickly are new discoveries regarding undeclared or poorly declared components of the formulations used by humans, and mixtures in foods or the natural environment, considered? What is the difference between the effects of the mixtures and those of the declared active ingredients alone at a biological, population or molecular level? We will try to address these questions and related ones.

We look forward to receiving your contributions. If you are interested, please indicate if you could send us the manuscript this year.

Prof. Dr. Gilles-Eric Seralini
Guest Editor

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Keywords

  • formulations
  • insecticides
  • herbicides
  • fungicides
  • long-term toxicity
  • ecosystem
  • advances in regulation
  • health
  • biodiversity

Published Papers (8 papers)

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Editorial

Jump to: Research, Review, Other

3 pages, 182 KiB  
Editorial
Pesticides in Formulations: New Revolutionary Findings
by Gilles-Eric Seralini
Toxics 2024, 12(2), 151; https://doi.org/10.3390/toxics12020151 - 15 Feb 2024
Cited by 2 | Viewed by 2542
Abstract
Everything began with the discovery that pesticides have long had unintended side effects on non-target species, which is illustrated by Ponepal et al [...] Full article

Research

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13 pages, 1398 KiB  
Article
Evaluation of the Morphological, Physiological and Biochemical Effects Induced by Coragen 20 SC in Some Non-Target Species
by Cristina Maria Ponepal, Liliana Cristina Soare, Oana-Alexandra Drăghiceanu, Cristina Florina Mihăescu, Nicoleta Anca Șuțan, Monica Marilena Țânțu and Alina Păunescu
Toxics 2023, 11(7), 618; https://doi.org/10.3390/toxics11070618 - 17 Jul 2023
Viewed by 1075
Abstract
Coragen 20 SC is an insecticide based on chlorantraniliprole that is applied on many crops. Considered an effective product with an incremental cost-benefit ratio, it has been widely used globally. Residual pesticides affect non-target organisms, so it is necessary to explore the possible [...] Read more.
Coragen 20 SC is an insecticide based on chlorantraniliprole that is applied on many crops. Considered an effective product with an incremental cost-benefit ratio, it has been widely used globally. Residual pesticides affect non-target organisms, so it is necessary to explore the possible effects induced by these xenobiotics on different species. This work aimed to assess some morphological, physiological and biochemical effects induced by Coragen 20 SC on two non-target species: Perca fluviatilis (Linné, 1758) and Triticum aestivum L. The concentrations used were the same for all tested species (0.0125, 0.025 and 0.05 mL L−1), and the experiments were of the acute, subchronic and chronic type. The toxicological effects of Coragen 20 SC on perch recorded behavioral changes, a decrease in respiratory rate and oxygen consumption, an increase in blood glucose levels and a decrease in the number of erythrocytes and leukocytes. The results obtained from the evaluation of Coragen 20 SC toxicity using the Triticum test indicate a weak to moderate phytotoxicity for the considered parameters at the applied doses. Only the assimilatory pigments were significantly modified at the concentration of 0.025 mL L−1 for the growth of the axial organs and the wet and dry weight, with the changes obtained not being statistically significant. Full article
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15 pages, 2467 KiB  
Article
Cytotoxicity Mechanisms of Eight Major Herbicide Active Ingredients in Comparison to Their Commercial Formulations
by Scarlett Ferguson, Robin Mesnage and Michael N. Antoniou
Toxics 2022, 10(11), 711; https://doi.org/10.3390/toxics10110711 - 21 Nov 2022
Cited by 2 | Viewed by 2599
Abstract
Commercial pesticide formulations contain co-formulants, which are generally considered as having no toxic effects in mammals. This study aims to compare the toxicity of 8 major herbicide active ingredients–namely glyphosate, dicamba, 2,4-D, fluroxypyr, quizalofop-p-ethyl, pendimethalin, propyzamide and metazachlor–with a typical commercial formulation of [...] Read more.
Commercial pesticide formulations contain co-formulants, which are generally considered as having no toxic effects in mammals. This study aims to compare the toxicity of 8 major herbicide active ingredients–namely glyphosate, dicamba, 2,4-D, fluroxypyr, quizalofop-p-ethyl, pendimethalin, propyzamide and metazachlor–with a typical commercial formulation of each active ingredient. Cytotoxicity and oxidative stress capability was assessed in human hepatoma HepG2 cells. Using an MTT assay, formulations of glyphosate (Roundup Probio), fluroxypyr (Hurler), quizalofop-p-ethyl (Targa Super) and dicamba (Hunter) were more toxic than the active ingredient alone. Metazachlor and its formulation Sultan had similar cytotoxicity profiles. Cytotoxicity profiles were comparable in immortalised human fibroblasts. Toxilight necrosis assays showed the formulation of metazachlor (Sultan50C) resulted in significant membrane disruption compared to the active ingredient. Generation of reactive oxygen species was detected for glyphosate, fluroxypyr, pendimethalin, quizalofop-p-ethyl, the formulation of 2,4-D (Anti-Liserons), and dicamba and its formulation Hunter. Further testing of quizalofop-p-ethyl and its formulation Targa Super in the ToxTracker assay system revealed that both products induced oxidative stress and an unfolded protein response. In conclusion, these results show that most herbicide formulations tested in this study are more toxic than their active ingredients in human tissue culture cell model systems. The results add to a growing body of evidence, which implies that commercial herbicide formulations and not just their active ingredients should be evaluated in regulatory risk assessment of pesticides. Full article
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16 pages, 4233 KiB  
Article
Petroleum in Pesticides: A Need to Change Regulatory Toxicology
by Gérald Jungers, Florence Portet-Koltalo, Julie Cosme and Gilles-Eric Seralini
Toxics 2022, 10(11), 670; https://doi.org/10.3390/toxics10110670 - 06 Nov 2022
Cited by 7 | Viewed by 3012
Abstract
Toxicological investigations of pesticides largely focus on the declared active ingredient, which constitutes only between a few percent to around 50% of the total formulation. The complete formulations are unknown. For each declared active ingredient, there are dozens or hundreds of formulations. We [...] Read more.
Toxicological investigations of pesticides largely focus on the declared active ingredient, which constitutes only between a few percent to around 50% of the total formulation. The complete formulations are unknown. For each declared active ingredient, there are dozens or hundreds of formulations. We demonstrate that petroleum has always been and is still always in pesticides. Gas chromatography and mass spectrometry (GC-MS) were applied for 24 pesticides. The measured compounds were the 16-priority polycyclic aromatic hydrocarbons (PAHs). The ratio of the PAHs to the threshold of toxicity was from 2.16 to 8288 times. The levels and distribution of PAHs per pesticide were different. Petroleum residues appear to be a waste product. The declared active component is taken alone for toxicity calculations, such as the acceptable daily intake (ADI). The PAHs with 2–3 cycles are more represented in pesticides than those with 4–6 cycles, which underlines that the petroleum residues appear to come mainly from crude unburned material. The ADI should be divided by 1000 if it is considered that petroleum residues amplify the toxicity by 1000. The admixture of PAHs in pesticides can be highly carcinogenic or toxic in the long term, even more than the declared active ingredient itself. Full article
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21 pages, 6471 KiB  
Article
A Mixture of Endocrine Disruptors and the Pesticide Roundup® Induce Oxidative Stress in Rabbit Liver When Administered under the Long-Term Low-Dose Regimen: Reinforcing the Notion of Real-Life Risk Simulation
by Periklis Vardakas, Aristidis S. Veskoukis, Danai Rossiou, Christos Gournikis, Theodora Kapetanopoulou, Vasiliki Karzi, Anca Oana Docea, Aristidis Tsatsakis and Demetrios Kouretas
Toxics 2022, 10(4), 190; https://doi.org/10.3390/toxics10040190 - 14 Apr 2022
Cited by 13 | Viewed by 3062
Abstract
Humans are exposed to xenobiotic mixtures daily through the long-term, low-dose regimen. Investigations designed to simulate this exposure profile approach the real-life risk simulation (RLRS) idea of modern toxicology. The purpose of the present study was to investigate the effects of 12-month exposure [...] Read more.
Humans are exposed to xenobiotic mixtures daily through the long-term, low-dose regimen. Investigations designed to simulate this exposure profile approach the real-life risk simulation (RLRS) idea of modern toxicology. The purpose of the present study was to investigate the effects of 12-month exposure of New Zealand rabbits to a xenobiotic mixture comprising seven endocrine disruptors (EDs), which are chemical substances raising great concerns for human health, as well as the herbicide glyphosate, and its commercial formulation Roundup®, on blood and tissues redox status. It is reported herein that at the systemic level, the administration of the EDs mixture induced perturbations of blood redox homeostasis at 3 months, whereas at 6 and 12 months, it activated redox adaptations. Contrariwise, exposure to glyphosate and Roundup®, individually, caused mainly disturbances of blood redox equilibrium. At the tissue level, particularly in the liver, the administration of both the EDs mixture and Roundup® induced oxidative stress, whereas glyphosate did not affect it. The RLRS notion appears to be confirmed through these findings. Indeed, the administration of the EDs mixture and Roundup®, under the long-term, low-dose regimen, elicited detrimental effects on the redox status of the liver, a crucial tissue with a valuable biological role in the detoxification of organisms from xenobiotics. Full article
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Review

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19 pages, 844 KiB  
Review
Poisoning Regulation, Research, Health, and the Environment: The Glyphosate-Based Herbicides Case in Canada
by Marie-Hélène Bacon, Louise Vandelac, Marc-André Gagnon and Lise Parent
Toxics 2023, 11(2), 121; https://doi.org/10.3390/toxics11020121 - 26 Jan 2023
Cited by 4 | Viewed by 6292
Abstract
Despite discourse advocating pesticide reduction, there has been an exponential increase in pesticide use worldwide in the agricultural sector over the last 30 years. Glyphosate-Based Herbicides (GBHs) are the most widely used pesticides on the planet as well as in Canada, where a [...] Read more.
Despite discourse advocating pesticide reduction, there has been an exponential increase in pesticide use worldwide in the agricultural sector over the last 30 years. Glyphosate-Based Herbicides (GBHs) are the most widely used pesticides on the planet as well as in Canada, where a total of almost 470 million kilograms of declared “active” ingredient glyphosate was sold between 2007 and 2018. GBHs accounted for 58% of pesticides used in the agriculture sector in Canada in 2017. While the independent scientific literature on the harmful health and environmental impacts of pesticides such as GBHs is overwhelming, Canada has only banned 32 “active” pesticide ingredients out of 531 banned in 168 countries, and reapproved GBHs in 2017 until 2032. This article, based on interdisciplinary and intersectoral research, will analyze how as a result of the scientific and regulatory captures of relevant Canadian agencies by the pesticide industry, the Canadian regulation and scientific assessment of pesticides are deficient and lagging behind other countries, using the GBH case as a basis for analysis. It will show how, by embracing industry narratives and biased evidence, by being receptive to industry demands, and by opaque decision making and lack of transparency, Health Canada’s Pest Management Regulatory Agency (PMRA) promotes commercial interests over the imperatives of public health and environmental protection. Full article
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14 pages, 304 KiB  
Review
Glyphosate, Roundup and the Failures of Regulatory Assessment
by Eva Novotny
Toxics 2022, 10(6), 321; https://doi.org/10.3390/toxics10060321 - 13 Jun 2022
Cited by 12 | Viewed by 6440
Abstract
Roundup is the most widely used herbicide in agriculture. It contains glyphosate as the ‘active ingredient’, together with formulants. There are various versions of Roundup, with somewhat different effects depending on the formulants. Most genetically-modified crops are designed to tolerate Roundup, thus allowing [...] Read more.
Roundup is the most widely used herbicide in agriculture. It contains glyphosate as the ‘active ingredient’, together with formulants. There are various versions of Roundup, with somewhat different effects depending on the formulants. Most genetically-modified crops are designed to tolerate Roundup, thus allowing spraying against weeds during the growing season of the crop without destroying it. Having been so heavily used, this herbicide is now found in the soil, water, air, and even in humans worldwide. Roundup may also remain as a residue on edible crops. Many studies have found harm to the environment and to health, making it imperative to regulate the use of Roundup and to ensure that its various formulations pose no danger when used in the long-term. Unfortunately, regulators may only assess the ‘active ingredient’, glyphosate, and ignore the toxicity of the formulants, which can be far more toxic than the active ingredient. This omission is in violation of a ruling by the Court of Justice of the European Union. There are close ties between the regulators and the industry they are supposed to regulate. Objectionable practices include ‘revolving doors’ between the regulators and the industry, heavy reliance on unpublished papers produced by the industry while dismissing papers published by independent scientists, and strong covert influence on the regulatory process by industry. Although this paper focuses on the European Union (EU), the situation is much the same in the United States. Full article

Other

10 pages, 612 KiB  
Study Protocol
In Vivo Estimation of the Biological Effects of Endocrine Disruptors in Rabbits after Combined and Long-Term Exposure: Study Protocol
by Vasiliki Karzi, Manolis N. Tzatzarakis, Athanasios Alegakis, Elena Vakonaki, Irene Fragkiadoulaki, Konstantinos Kaloudis, Christina Chalkiadaki, Paraskevi Apalaki, Maria Panagiotopoulou, Aikaterini Kalliantasi, Demetrios Kouretas, Anca Oana Docea, Daniela Calina and Aristidis Tsatsakis
Toxics 2022, 10(5), 246; https://doi.org/10.3390/toxics10050246 - 12 May 2022
Cited by 7 | Viewed by 2208
Abstract
Recently, an increasing number of chemical compounds are being characterized as endocrine disruptors since they have been proven to interact with the endocrine system, which plays a crucial role in the maintenance of homeostasis. Glyphosate is the active substance of the herbicide Roundup [...] Read more.
Recently, an increasing number of chemical compounds are being characterized as endocrine disruptors since they have been proven to interact with the endocrine system, which plays a crucial role in the maintenance of homeostasis. Glyphosate is the active substance of the herbicide Roundup®, bisphenol A (BPA) and di (2-ethylhexyl) phthalate (DEHP) are used as plasticizers, while triclosan (TCS), methyl (MePB), propyl (PrPB), and butyl (BuPB) parabens are used as antimicrobial agents and preservatives mainly in personal care products. Studies indicate that exposure to these substances can affect humans causing developmental problems and problems in the endocrine, reproductive, nervous, immune, and respiratory systems. Although there are copious studies related to these substances, there are few in vivo studies related to combined exposure to these endocrine disruptors. The aim of the present pilot study is the investigation and assessment of the above substances’ toxicity in rabbits after twelve months of exposure to glyphosate (both pure and commercial form) and to a mixture of all the above substances at subtoxic levels. The lack of data from the literature concerning rabbits’ exposure to these substances and the restrictions of the 3Rs Principle will result in a limited number of animals available for use (four animals per group, twenty animals in total). Full article
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