Effects of co-formulants on the absorption and secretion of active substances in plant protection products in vitro
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| Názov: | Effects of co-formulants on the absorption and secretion of active substances in plant protection products in vitro |
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| Autori: | Benjamin Fischer, Christian Tobias Willenbockel, Denise Bloch, P. Marx-Stoelting, Mawien Karaca, Tewes Tralau |
| Zdroj: | Arch Toxicol |
| Informácie o vydavateľovi: | Springer Science and Business Media LLC, 2021. |
| Rok vydania: | 2021 |
| Predmety: | 0301 basic medicine, Insecticides, 0303 health sciences, Ivermectin, Herbicides, mixture effects, Biological Availability, Fluorescence Polarization, pesticides, Surface-Active Agents/chemistry [MeSH], Glycolates/pharmacokinetics [MeSH], Fluorescence Polarization [MeSH], Pesticides, Herbicides/administration, Ivermectin/pharmacokinetics [MeSH], Toxicokinetic, Ivermectin/toxicity [MeSH], Ivermectin/administration, Co-formulants, Surfactants, Toxicokinetics and Metabolism, Caco-2 Cells [MeSH], Insecticides/pharmacokinetics [MeSH], Tandem Mass Spectrometry [MeSH], Ivermectin/analogs, Herbicides/pharmacokinetics [MeSH], Herbicides/toxicity [MeSH], Humans [MeSH], Mixture effects, Plant protection products, Chromatography, Liquid [MeSH], Insecticides/toxicity [MeSH], Glycolates/toxicity [MeSH], Glycolates/administration, Biological Availability [MeSH], Insecticides/administration, surfactants, toxicokinetic, Glycolates, Surface-Active Agents, plant protection products, 03 medical and health sciences, Tandem Mass Spectrometry, Humans, co-formulants, Caco-2 Cells, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit, Chromatography, Liquid |
| Popis: | Currently, the authorisation process for plant protection products (PPPs) relies on the testing of acute and topological toxicity only. Contrastingly, the evaluation of active substances includes a more comprehensive set of toxicity studies. Nevertheless, mixture effects of active ingredients and co-formulants may result in increased toxicity. Therefore, we investigated effects of surface active co-formulants on the toxicity of two PPPs focussing on qualitative and quantitative toxicokinetic effects on absorption and secretion. The respective products are based on the active substances abamectin and fluroxypyr-meptyl and were tested for cytotoxicity in the presence or absence of the corresponding surfactants and co-formulants using Caco-2 cells. In addition, the effect of co-formulants on increased cellular permeation was quantified using LC–MS/MS, while potential kinetic mixture effects were addressed by fluorescence anisotropy measurements and ATPase assays. The results show that surface active co-formulants significantly increase the cytotoxicity of the investigated PPPs, leading to more than additive mixture effects. Moreover, analytical investigations show higher efflux ratios of both active substances and the metabolite fluroxypyr upon combination with certain concentrations of the surfactants. The results further point to a significant and concentration-dependent inhibition of Pgp transporters by most of the surfactants as well as to increased membrane fluidity. Altogether, these findings strongly support the hypothesis that surfactants contribute to increased cytotoxicity of PPPs and do so by increasing the bioavailability of the respective active substances. |
| Druh dokumentu: | Article Other literature type |
| Jazyk: | English |
| ISSN: | 1432-0738 0340-5761 |
| DOI: | 10.1007/s00204-021-03140-x |
| DOI: | 10.14279/depositonce-17243 |
| Prístupová URL adresa: | https://link.springer.com/content/pdf/10.1007/s00204-021-03140-x.pdf https://pubmed.ncbi.nlm.nih.gov/34417632 https://link.springer.com/article/10.1007/s00204-021-03140-x https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8448693 https://www.ncbi.nlm.nih.gov/pubmed/34417632 https://link.springer.com/content/pdf/10.1007/s00204-021-03140-x.pdf https://repository.publisso.de/resource/frl:6451649 |
| Rights: | CC BY URL: http://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (http://creativecommons.org/licenses/by/4.0/) . |
| Prístupové číslo: | edsair.doi.dedup.....144ae46e6bd1284e9ba32ae39a3dc8bc |
| Databáza: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstrakt: | Currently, the authorisation process for plant protection products (PPPs) relies on the testing of acute and topological toxicity only. Contrastingly, the evaluation of active substances includes a more comprehensive set of toxicity studies. Nevertheless, mixture effects of active ingredients and co-formulants may result in increased toxicity. Therefore, we investigated effects of surface active co-formulants on the toxicity of two PPPs focussing on qualitative and quantitative toxicokinetic effects on absorption and secretion. The respective products are based on the active substances abamectin and fluroxypyr-meptyl and were tested for cytotoxicity in the presence or absence of the corresponding surfactants and co-formulants using Caco-2 cells. In addition, the effect of co-formulants on increased cellular permeation was quantified using LC–MS/MS, while potential kinetic mixture effects were addressed by fluorescence anisotropy measurements and ATPase assays. The results show that surface active co-formulants significantly increase the cytotoxicity of the investigated PPPs, leading to more than additive mixture effects. Moreover, analytical investigations show higher efflux ratios of both active substances and the metabolite fluroxypyr upon combination with certain concentrations of the surfactants. The results further point to a significant and concentration-dependent inhibition of Pgp transporters by most of the surfactants as well as to increased membrane fluidity. Altogether, these findings strongly support the hypothesis that surfactants contribute to increased cytotoxicity of PPPs and do so by increasing the bioavailability of the respective active substances. |
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| ISSN: | 14320738 03405761 |
| DOI: | 10.1007/s00204-021-03140-x |