Evidence of in vitro metabolic interaction effects of a chlorfenvinphos, ethion and linuron mixture on human hepatic detoxification rates
| Autor: | Georges de Sousa, Roger Rahmani, Henri Wortham, Ludovic Peyre, Ali Kadar, Pierre Doumenq |
|---|---|
| Přispěvatelé: | ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Ecole d'Ingénieurs de Purpan (INP - PURPAN), Université de Toulouse (UT)-Université de Toulouse (UT), Laboratoire Chimie de l'environnement (LCE), Aix Marseille Université (AMU)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU)-Institut de Chimie du CNRS (INC), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées |
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Health Toxicology and Mutagenesis [SDV]Life Sciences [q-bio] toxicologie alimentaire 010501 environmental sciences Pharmacology Ethion human health 01 natural sciences Toxicology chemistry.chemical_compound Cytochrome P-450 Enzyme System hepatic clearance Linuron media_common 2. Zero hunger Chemistry Chlorfenvinphos General Medicine santé humaine Pollution Liver liver function Inactivation Metabolic metabolic interactions toxin inactivation Microsomes Liver Detoxification risque pour la santé Environmental Engineering Metabolic Clearance Rate pesticides mixture détoxification 03 medical and health sciences Health risk assessment Animals Humans Environmental Chemistry media_common.cataloged_instance Pesticides European union pesticide 0105 earth and related environmental sciences Pesticide residue interaction métabolique fonction hépatique Public Health Environmental and Occupational Health Organothiophosphorus Compounds General Chemistry Pesticide 030104 developmental biology 13. Climate action Hepatocytes Liver function |
| Zdroj: | Chemosphere Chemosphere, 2017, 181, pp.666-674. ⟨10.1016/j.chemosphere.2017.04.116⟩ Chemosphere, Elsevier, 2017, 181, pp.666-674. ⟨10.1016/j.chemosphere.2017.04.116⟩ |
| ISSN: | 0045-6535 |
| DOI: | 10.1016/j.chemosphere.2017.04.116⟩ |
| Popis: | General population exposure to pesticides mainly occurs via food and water consumption. However, their risk assessment for regulatory purposes does not currently consider the actual co-exposure to multiple substances. To address this concern, relevant experimental studies are needed to fill the lack of data concerning effects of mixture on human health. For the first time, the present work evaluated on human microsomes and liver cells the combined metabolic effects of, chlorfenvinphos, ethion and linuron, three pesticides usually found in vegetables of the European Union. Concentrations of these substances were measured during combined incubation experiments, thanks to a new analytical methodology previously developed. The collected data allowed for calculation and comparison of the intrinsic hepatic clearance of each pesticide from different combinations. Finally, the results showed clear inhibitory effects, depending on the association of the chemicals at stake. The major metabolic inhibitor observed was chlorfenvinphos. During co-incubation, it was able to decrease the intrinsic clearance of both linuron and ethion. These latter also showed a potential for metabolic inhibition mainly cytochrome P450-mediated in all cases. Here we demonstrated that human detoxification from a pesticide may be severely hampered in case of co-occurrence of other pesticides, as it is the case for drugs interactions, thus increasing the risk of adverse health effects. These results could contribute to improve the current challenging risk assessment of human and animal dietary to environmental chemical mixtures. |
| Databáze: | OpenAIRE |
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