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1. Nonterpenoid Chemical Diversity of Cannabis Phenotypes Predicts Differentiated Aroma Characteristics

Author: Twinkle R. Paryani, Manuel E. Sosa, Michael F. Z. Page, Thomas J. Martin, Melissa V. Hearvy, Marcos A. Ojeda, Kevin A. Koby, Jonathan J. Grandy, Bradley G. Melshenker, Ian Skelly, and Iain W. H. Oswald
Subjects: Chemistry, QD1-999
Published: 2024
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2. Minor, Nonterpenoid Volatile Compounds Drive the Aroma Differences of Exotic Cannabis

Author: Iain W. H. Oswald, Twinkle R. Paryani, Manuel E. Sosa, Marcos A. Ojeda, Mark R. Altenbernd, Jonathan J. Grandy, Nathan S. Shafer, Kim Ngo, Jack R. Peat, Bradley G. Melshenker, Ian Skelly, Kevin A. Koby, Michael F. Z. Page, and Thomas J. Martin
Subjects: Chemistry, QD1-999
Published: 2023
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3. Photophysical Properties of Anthracene Derivatives

Author: Agonist Kastrati, Franck Oswald, Antoine Scalabre, and Katharina M. Fromm
Subjects: anthracene, light, spectra, electron, photopysics, emission, Chemistry, QD1-999
Abstract: In this tutorial review, we intend to provide the reader with a comprehensive introduction to the photophysical properties of organic compounds with a specific focus on anthracene and its derivatives. Anthracene-based building blocks have attracted the attention of chemists due to their intrinsic luminescent properties. A deep understanding of their interaction with light, including the mechanisms of emission (luminescence, i.e., fluorescence or phosphorescence) and quenching, is crucial to design and generate compounds with precise properties for further applications. Thus, the photophysical properties of different types of aggregates, both in the ground state (J- and H-type) and in the exited state (e.g., excimer, exciplex) will be discussed, finishing with a few examples of dyads and triads.
Published: 2023
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4. Efficient, Stable, and Solvent‐Free Synthesized Single‐Atom Catalysts: Carbonized Transition Metal‐Doped ZIF‐8 for the Hydrogen Evolution Reaction

Author: Dr. Robin N. Dürr, Emma Stéphan, Jocelyne Leroy, Dr. Frédéric Oswald, Bénédicte Verhaeghe, and Dr. Bruno Jousselme
Subjects: single-atom catalyst, hydrogen evolution reaction, solvent-free synthesis, transition metal-doped ZIF-8, electrocatalysis, Industrial electrochemistry, TP250-261, Chemistry, QD1-999
Abstract: Abstract Herein we present non‐noble metal single‐atom catalysts (SACs) based on carbonized transition metal‐doped zeolitic imidazolate frameworks (ZIFs) as stable and efficient electrocatalysts for the hydrogen evolution reaction in acidic media. In this work, earth‐abundant metals are embedded in a porous N‐rich carbon matrix by pyrolyzing metal‐doped ZIF structures and characterized by spectroscopic, microscopic, and electrochemical methods. The complete synthesis of these high surface area SACs was carried out without any solvents and hence offers a promising route for a more sustainable catalyst production and industrial upscaling. As the best‐performing catalyst, cobalt SAC illustrated already with a low cobalt loading of
Published: 2023
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5. Cross-View Outdoor Localization in Augmented Reality by Fusing Map and Satellite Data

Author: René Emmaneel, Martin R. Oswald, Sjoerd de Haan, and Dragos Datcu
Subjects: augmented reality, visual positioning, outdoor localization, maps, satellite data, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract: Visual positioning is the task of finding the location of a given image and is necessary for augmented reality applications. Traditional algorithms solve this problem by matching against premade 3D point clouds or panoramic images. Recently, more attention has been given to models that match the ground-level image with overhead imagery. In this paper, we introduce AlignNet, which builds upon previous work to bridge the gap between ground-level and top-level images. By making multiple key insights, we push the model results to achieve up to 4 times higher recall rates on a visual position dataset. We use a fusion of both satellite and map data from OpenStreetMap for this matching by extending the previously available satellite database with corresponding map data. The model pushes the input images through a two-branch U-Net and is able to make matches using a geometric projection module to map the top-level image to the ground-level domain at a given position. By calculating the difference between the projection and ground-level image in a differentiable fashion, we can use a Levenberg–Marquardt (LM) module to iteratively align the estimated position towards the ground-truth position. This sample-wise optimization strategy allows the model to align the position better than if the model has to obtain the location in a single step. We provide key insights into the model’s behavior, which allows us to increase the model’s ability to obtain competitive results on the KITTI cross-view dataset. We compare our obtained results with the state of the art and obtain new best results on 3 of the 9 categories we look at, which include a 57% likelihood of lateral localization within 1 m in a 40 m × 40 m area and a 93% azimuth localization within 3∘ when using a 20∘ rotation noise prior.
Published: 2023
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6. Life Cycle Assessment for Substitutive Building Materials Using the Example of the Vietnamese Road Sector

Author: Petra Schneider, Naveedh Ahmed, Florin-Constantin Mihai, Anna Belousova, Radek Kucera, Klaus-Dieter Oswald, Thomas Lange, and Anh Le Hung
Subjects: life-cycle assessment, substitutive building materials, secondary building materials, road subbase material, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract: Road construction usually relies on the utilization of natural aggregates as building materials. However, increasing pressure for sustainable roads highlights the importance of replacing natural materials with industrial byproducts. The scope of the present study was to identify feasible secondary raw materials for road subbase construction, and to investigate their environmental footprint in the context of Vietnam. This work examines road subbase alternatives such as manufactured sand (m-sand), granulated blast furnace slag (GBF), electric arc furnace slag (EAF), construction and demolition waste (CDW), and fly ash (FA). Based on the life-cycle assessment (LCA) approach, the environmental footprints of the alternative waste-based layers were compared with one another and with the corresponding conventional layers. The study comprises following working steps: (i) a comprehensive literature review of the respective materials, (ii) general chemical and soil mechanical analysis of road subbase substitutes, and (iii) LCA of the material alternatives in the context of the Vietnamese road construction sector. The results for the road subbase layer indicated that CDW and FA had lower impacts—particularly in the impact categories global warming potential and mineral resource scarcity. The overall LCA analysis for the road subbase layer highlighted that the greatest footprint contribution was involved in the construction material transportation processes. Thus, sourcing of materials closer to the site or the use of low-emission transport alternatives is needed.
Published: 2023
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7. The Effect of C60 and Pentacene Adsorbates on the Electrical Properties of CVD Graphene on SiO2

Author: Jacopo Oswald, Davide Beretta, Michael Stiefel, Roman Furrer, Dominique Vuillaume, and Michel Calame
Subjects: organic, semiconductor, graphene, field effect, transistor, van der Waals, Chemistry, QD1-999
Abstract: Graphene is an excellent 2D material for vertical organic transistors electrodes due to its weak electrostatic screening and field-tunable work function, in addition to its high conductivity, flexibility and optical transparency. Nevertheless, the interaction between graphene and other carbon-based materials, including small organic molecules, can affect the graphene electrical properties and therefore, the device performances. This work investigates the effects of thermally evaporated C60 (n-type) and Pentacene (p-type) thin films on the in-plane charge transport properties of large area CVD graphene under vacuum. This study was performed on a population of 300 graphene field effect transistors. The output characteristic of the transistors revealed that a C60 thin film adsorbate increased the graphene hole density by (1.65 ± 0.36) × 1012 cm−2, whereas a Pentacene thin film increased the graphene electron density by (0.55 ± 0.54) × 1012 cm−2. Hence, C60 induced a graphene Fermi energy downshift of about 100 meV, while Pentacene induced a Fermi energy upshift of about 120 meV. In both cases, the increase in charge carriers was accompanied by a reduced charge mobility, which resulted in a larger graphene sheet resistance of about 3 kΩ at the Dirac point. Interestingly, the contact resistance, which varied in the range 200 Ω–1 kΩ, was not significantly affected by the deposition of the organic molecules.
Published: 2023
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8. Hydrogel Encapsulation of Genome-Engineered Stem Cells for Long-Term Self-Regulating Anti-Cytokine Therapy

Author: Kelsey H. Collins, Lara Pferdehirt, Leila S. Saleh, Alireza Savadipour, Luke E. Springer, Kristin L. Lenz, Dominic M. Thompson, Sara J. Oswald, Christine T. N. Pham, and Farshid Guilak
Subjects: induced pluripotent stem cells, implant, drug delivery, rheumatoid arthritis, autoimmune, designer cells, Science, Chemistry, QD1-999, Inorganic chemistry, QD146-197, General. Including alchemy, QD1-65
Abstract: Biologic therapies have revolutionized treatment options for rheumatoid arthritis (RA) but their continuous administration at high doses may lead to adverse events. Thus, the development of improved drug delivery systems that can sense and respond commensurately to disease flares represents an unmet medical need. Toward this end, we generated induced pluripotent stem cells (iPSCs) that express interleukin-1 receptor antagonist (IL-1Ra, an inhibitor of IL-1) in a feedback-controlled manner driven by the macrophage chemoattractant protein-1 (Ccl2) promoter. Cells were seeded in agarose hydrogel constructs made from 3D printed molds that can be injected subcutaneously via a blunt needle, thus simplifying implantation of the constructs, and the translational potential. We demonstrated that the subcutaneously injected agarose hydrogels containing genome-edited Ccl2-IL1Ra iPSCs showed significant therapeutic efficacy in the K/BxN model of inflammatory arthritis, with nearly complete abolishment of disease severity in the front paws. These implants also exhibited improved implant longevity as compared to the previous studies using 3D woven scaffolds, which require surgical implantation. This minimally invasive cell-based drug delivery strategy may be adapted for the treatment of other autoimmune or chronic diseases, potentially accelerating translation to the clinic.
Published: 2023
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9. Intestinal toxicity of the new type A trichothecenes, NX and 3ANX

Author: Sylvie Puel, J. David Miller, Laura Soler, Isabelle P. Oswald, Yannick Lippi, Manon Neves, Alix Pierron, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), 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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Transcriptomic impact of Xenobiotics (E23 TRiX), Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Carleton College, This research was supported in part by the ANR grant 'Newmyco' (ANR-15-CE21-0010), the ANR grant 'EmergingMyco' (ANR-18-CE34-0014) and the Ontario Ministry of Food and Agriculture (FS2015-2617/SF6115)., ANR-15-CE21-0010,Newmyco,Metabolome de deux contaminants fongiques du blé d'importance majeure: identification de nouveaux métabolites toxiques(2015), ANR-18-CE34-0014,EmergingMyco,Les mycotoxines émergentes : un nouveau risque pour l'Homme et les animaux ?(2018), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse)
Subjects: Fusarium, Environmental Engineering, Swine, Health, Toxicology and Mutagenesis, Cell, Explant, Trichothecenes, Type A, Transcriptome, 03 medical and health sciences, Immune system, medicine, Environmental Chemistry, Animals, Humans, Gut, Intestinal Mucosa, 030304 developmental biology, 0303 health sciences, biology, Cell growth, Chemistry, Gene Expression Profiling, 030302 biochemistry & molecular biology, Public Health, Environmental and Occupational Health, General Medicine, General Chemistry, biology.organism_classification, Pollution, Molecular biology, Deoxynivalenol, 3. Good health, Fusarium graminearum, medicine.anatomical_structure, Vacuolization, Apoptosis, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Toxicity, Caco-2 Cells, Trichothecenes
Abstract: International audience; NX and its acetylated form 3ANX are two new type A trichothecenes produced by Fusarium graminearum whose toxicity is poorly documented. The aim of this study was to obtain a general view of the intestinal toxicity of these toxins. Deoxynivalenol (DON), which differs from NX by the keto group at C8, served as a benchmark. The viability of human intestinal Caco-2 cells decreased after 24 h of exposure to 3 μM NX (−21.4%), 3 μM DON (−20.2%) or 10 μM 3ANX (−17.4%). Histological observations of porcine jejunal explants exposed for 4 h to 10 μM of the different toxins showed interstitial edema and cellular debris. Explants exposed to NX also displayed cell vacuolization, a broken epithelial barrier and high loss of villi. Whole transcriptome profiling revealed that NX, DON and 3ANX modulated 369, 146 and 55 genes, respectively. Functional analyses indicated that the three toxins regulate the same gene networks and signaling pathways mainly; cell proliferation, differentiation, apoptosis and growth, and particularly immune and pro-inflammatory responses. Greater transcriptional impacts were observed with NX than with DON. In conclusion, our data revealed that the three toxins have similar impacts on the intestine but of different magnitude: NX > DON ≫ 3ANX. NX and 3ANX should consequently be included in overall risk analysis linked to the presence of trichothecenes in our diet.
Published: 2022
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10. Effects of Fusarium metabolites beauvericin and enniatins alone or in mixture with deoxynivalenol on weaning piglets

Author: Isabelle P. Oswald, Barbara Novak, Caroline Emsenhuber, Dian Schatzmayr, Amanda Lopes Hasuda, Ana Paula Frederico Rodrigues Loureiro Bracarense, Viviane Mayumi Maruo, Manon Neves, Mahdi Ghanbari, Philippe Pinton, Silvia Wein, Biomin Research Center, State University of Londrina = Universidade Estadual de Londrina, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), 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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Universidade Federal do Tocantins (UFT), Universidade Federal do Tocantins, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), This research was funded by Austrian Research Promotion Agency (FFG) via the research project Early Stage, grant number 879467 and by the French ANR project 'EmergingMyco' (ANR-18-CE34-0014). Amanda L. Hasuda received a fellowship from the Coordenaç˜ao de Aperfeiçoamento de Pessoal de Nível Superior-CAPES/Cofecub (Grant 0389/2019). This study was financed in part by the Coordenaç˜ao de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES) - FinanceCode 001., and ANR-18-CE34-0014,EmergingMyco,Les mycotoxines émergentes : un nouveau risque pour l'Homme et les animaux ?(2018)
Subjects: Fusarium, Swine, [SDV]Life Sciences [q-bio], Weaning, Gut microbiota, Gut flora, Toxicology, Weight Gain, Jejunum, 03 medical and health sciences, chemistry.chemical_compound, Eating, Animal science, Depsipeptides, medicine, Animals, Mycotoxin, 030304 developmental biology, 0303 health sciences, biology, 030306 microbiology, food and beverages, General Medicine, Mycotoxins, biology.organism_classification, Biomarker of effect, Beauvericin, 3. Good health, Gastrointestinal Microbiome, Intestines, medicine.anatomical_structure, chemistry, Liver, Fungal metabolites, Lymph, medicine.symptom, Trichothecenes, Weight gain, Histological alterations, Cyclic hexadepsipeptides, Food Science
Abstract: International audience; The impact of the Fusarium-derived metabolites beauvericin, enniatin B and B1 (EB) alone or in combination with deoxynivalenol (DON) was investigated in 28-29 days old weaning piglets over a time period of 14 days. The coapplication of EB and DON (EB + DON) led to a significant decrease in the weight gain of the animals. Liver enzyme activities in plasma were significantly decreased at day 14 in piglets receiving the EB + DON-containing diet compared to piglets receiving the control diet. All mycotoxin-contaminated diets led to moderate to severe histological lesions in the jejunum, the liver and lymph nodes. Shotgun metagenomics revealed a significant effect of EB-application on the gut microbiota. Our results provide novel insights into the harmful impact of emerging mycotoxins alone or with DON on the performance, gut health and immunological parameters in pigs.
Published: 2021
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11. Versicolorin A enhances the genotoxicity of aflatoxin B1 in human liver cells by inducing the transactivation of the Ah-receptor

Author: Clémence Budin, Sylvie Puel, Abraham Brouwer, Laura Soler, Barbara M.A. van Vugt-Lussenburg, Hai-Yen Man, Bart van der Burg, Isabelle P. Oswald, Carine Al-Ayoubi, VU University Amsterdam, BioDetection Systems, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), 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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Animal Ecology, and Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU)
Subjects: Transcriptional Activation, Aflatoxin, Aflatoxin B1, [SDV]Life Sciences [q-bio], Metabolite, Cytotoxicity, Anthraquinones, Toxicology, medicine.disease_cause, 03 medical and health sciences, chemistry.chemical_compound, Transactivation, 0404 agricultural biotechnology, Cytochrome P-450 Enzyme System, SDG 3 - Good Health and Well-being, hemic and lymphatic diseases, Basic Helix-Loop-Helix Transcription Factors, Versicolorin A, medicine, Humans, Mycotoxin, Carcinogen, 030304 developmental biology, 0303 health sciences, biology, Chemistry, AhR, Cytochrome P450, Drug Synergism, Hep G2 Cells, 04 agricultural and veterinary sciences, General Medicine, Mycotoxins, Aryl hydrocarbon receptor, 040401 food science, 3. Good health, Receptors, Aryl Hydrocarbon, Biochemistry, biology.protein, Genotoxicity, Mutagens, Food Science
Abstract: International audience; Aflatoxins are a group of mycotoxins that have major adverse effects on human health. Aflatoxin B1 (AFB1) is the most important aflatoxin and a potent carcinogen once converted into a DNA-reactive form by cytochrome P450 enzymes (CYP450). AFB1 biosynthesis involves the formation of Versicolorin A (VerA) which shares structural similarities with AFB1 and can be found in contaminated commodities, often co-occurring with AFB1. This study investigated and compared the toxicity of VerA and AFB1, alone or in combination, in HepG2 human liver cells. Our results show that both toxins have similar cytotoxic effects and are genotoxic although, unlike AFB1, the main genotoxic mechanism of VerA does not involve the formation of DNA double-strand breaks. Additionally, we show that VerA activates the aryl hydrocarbon receptor (AhR) and significantly induce the expression of the CYP450-1A1 (CYP1A1) while AFB1 did not induce AhR-dependent CYP1A1 activation. Combination of VerA with AFB1 resulted in enhanced genotoxic effects, suggesting that AhR-activation by VerA influences AFB1 genotoxicity by promoting its bioactivation by CYP450s to a highly DNA-reactive metabolite. Our results emphasize the need for expanding the toxicological knowledge regarding mycotoxin biosynthetic precursors to identify those who may pose, directly or indirectly, a threat to human health.
Published: 2021
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12. A review on combined effects of moniliformin and co-occurring Fusarium toxins in farm animals

Author: Jean-Marc Fremy, Isabelle P. Oswald, H.P. van Egmond, Imourana Alassane-Kpembi, Bruce Cottrill, Independent, ToxAlim (ToxAlim), 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), Institut National Polytechnique (Toulouse) (Toulouse INP), 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), Hôpital d'Instruction des Armées Camp Guézo, Service de Santé des Armées, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3)
Subjects: animal structures, deoxynivalenol, Biology, Toxicology, 01 natural sciences, chemistry.chemical_compound, 0404 agricultural biotechnology, Co occurring, [SDV.IDA]Life Sciences [q-bio]/Food engineering, Fusarium toxins, Food science, Mycotoxin, fumonisin B-1, Fumonisin B1, feed, 010401 analytical chemistry, Public Health, Environmental and Occupational Health, risk assessment, food and beverages, 04 agricultural and veterinary sciences, 040401 food science, 0104 chemical sciences, chemistry, [SDV.TOX]Life Sciences [q-bio]/Toxicology, adverse effects, Moniliformin, Food Science
Abstract: Co-occurrence of mycotoxins in food and feed represents the rule rather than the exception. Information about combinatory toxic effects of co-occurring mycotoxins is scarce, in particular the effects that mixtures of mycotoxins in feed may have on farm animals. This review focusses on studies on the combined effects of moniliformin and co-occurring mycotoxins in feed on farm animals. Moniliformin is a mycotoxin of emerging scientific interest, which may co-occur with many other mycotoxins, especially Fusarium mycotoxins. Oral exposure to moniliformin reduces feed consumption and body weight gain in poultry, in pigs and catfish, and induces cardiotoxic effects and/or alterations in serum biochemical and haematological parameters. In this review only experiments comparing effects as a result of the exposure to a combination of mycotoxins with effects due to the exposure to single mycotoxins were considered. Identified published studies on combined toxicity have been limited to combinations of moniliformin with either fumonisin B1 or deoxynivalenol, and were performed with poultry, pigs, and catfish. Most of the moniliformin/fumonisin B1 investigations involved poultry and focussed on adverse effects on feed intake, weight gain and immune response, as well as organ lesions. These studies mainly reported an interactive toxicity of moniliformin and fumonisin B1 but did not allow identification of the type of interaction. Likewise, no indication could be given for the interaction detected for both mycotoxins on weight gains of catfish. For the moniliformin/deoxynivalenol combination, only one study with broiler chickens was found relevant. This study concluded additive or less than additive toxicity, using kidney lesions and renal tubular epithelial degeneration as endpoints. While possible interactions between moniliformin and fumonisin B1 or deoxynivalenol were identified, the conclusions are based on limited studies and experimental designs. Further studies on the combined toxicity of moniliformin with other mycotoxins and other animal species would be needed.
Published: 2019
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13. Morphologic, molecular and metabolic characterization of Aspergillus section Flavi in spices marketed in Lebanon

Author: A. Querin, Sophie Lorber, Monzer Hamze, Jean-Denis Bailly, Soraya Tadrist, Amaranta Carvajal-Campos, Sylviane Bailly, Joya Makhlouf, Olivier Puel, Isabelle P. Oswald, ToxAlim (ToxAlim), 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), Institut National Polytechnique (Toulouse) (Toulouse INP), 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), Lebanese University [Beirut] (LU), Génotoxicité & Signalisation (ToxAlim-GS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc)
Subjects: 0301 basic medicine, Aflatoxin, Veterinary medicine, Indoles, [SDV]Life Sciences [q-bio], lcsh:Medicine, Food Contamination, Aspergillus flavus, Biology, Article, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Aflatoxins, Lebanon, Spices, Mycotoxin, lcsh:Science, Phylogeny, health care economics and organizations, Aspergillus, Multidisciplinary, lcsh:R, food and beverages, Mycotoxins, biology.organism_classification, Molecular analysis, 030104 developmental biology, chemistry, lcsh:Q, 030217 neurology & neurosurgery, Food contaminant
Abstract: Spices are used extensively in Lebanon not only to flavour foods but also for their medicinal properties. To date, no data are available regarding the nature of the toxigenic fungal species that may contaminate these products at the marketing stage in this country. Eighty samples corresponding to 14 different types of spices were collected throughout Lebanon to characterize the Aspergillus section Flavi contaminating spices marketed in Lebanon and the toxigenic potential of these fungal species. Most fungal genera and species were identified as belonging to Aspergillus section Flavi. Aspergillus flavus was the most frequent species, representing almost 80% of the isolates. Although identified as A. flavus by molecular analysis, some strains displayed atypical morphological features. Seven strains of A. tamarii and one A. minisclerotigenes were also isolated. Analyses of toxigenic potential demonstrated that almost 80% of strains were able to produce mycotoxins, 47% produced aflatoxins, and 72% produced cyclopiazonic acid, alone or in combination with aflatoxins.
Published: 2019
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14. Individual and combined cytotoxicity of major trichothecenes type B, deoxynivalenol, nivalenol, and fusarenon-X on Jurkat human T cells

Author: Imourana Alassane-Kpembi, Amnart Poapolathep, Patchara Phuektes, Saranya Poapolathep, Sawinee Aupanun, Isabelle P. Oswald, Kasetsart University (KU), Khon Kaen University [Thailand] (KKU), ToxAlim (ToxAlim), 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), Institut National Polytechnique (Toulouse) (Toulouse INP), 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), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and Center for Advanced Studies for Agriculture and Food, Institute for Advanced Studies, Kasetsart University under the Higher Education Research Promotion and National Research University Project of Thailand, Office of the Higher Education Commission, Ministry of Education, Thailand
Subjects: Cell Survival, deoxynivalenol, fusarenon-X, Apoptosis, 010501 environmental sciences, Pharmacology, Toxicology, 01 natural sciences, Jurkat cells, jurkat T cell, Inhibitory Concentration 50, Jurkat Cells, 03 medical and health sciences, chemistry.chemical_compound, Humans, MTT assay, Mycotoxin, Cytotoxicity, IC50, nivalenol, 030304 developmental biology, 0105 earth and related environmental sciences, 0303 health sciences, Dose-Response Relationship, Drug, Drug Synergism, Flow Cytometry, 3. Good health, chemistry, mycotoxin combination, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Toxicity, Biological Assay, Trichothecenes, Antagonism
Abstract: International audience; Food and feed commodities are often contaminated by more than one mycotoxin. Among the several combinations that frequently occur, fusariotoxins are often mentioned. The multi-mycotoxins contamination is a serious threat for health. In the present study we investigated the toxic interactions between deoxynivalenol (DON), nivalenol (NIV), and fusarenon-X (FX) in Jurkat T cells by using the MTT assay. The tested mycotoxins alone or in combination had a dose dependent effect on proliferating lymphocytes. According to IC50, it could be classified in decreasing order of toxicity: FX > NIV > DON > DON + FX > NIV + FX > DON + NIV > DON + NIV + FX. The type of mycotoxin interactions was assessed by calculating the combination index (CI) and the dose reduction index (DRI). Our data indicate that an antagonistic effect was strongly observed in binary combination between DON and NIV at higher concentrations and ternary mixtures. Meanwhile, the DON and FX mixtures generated moderate antagonism, while NIV and FX provoked different interactions. The effects of tested mycotoxins on apoptosis were also determined using a FACScan flow cytometer. At IC75, the percentages of apoptotic cells in all treatment groups were significantly different when compared to control group but no significant differences among treatment groups was observed. Taken together, our data suggest that immunotoxicity among multi-mycotoxins contamination cannot be predicted based on individual effects but depends on the mixtures, ratio and/or concentrations in the product, as well as type of target cells.
Published: 2019
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15. Statistical Integration of ‘Omics Data Increases Biological Knowledge Extracted from Metabolomics Data: Application to Intestinal Exposure to the Mycotoxin Deoxynivalenol

Author: Marie Tremblay-Franco, Claire Naylies, Imourana Alassane-Kpembi, Cécile Canlet, Philippe Pinton, Yannick Lippi, Isabelle P. Oswald, Roselyne Gautier, Manon Neves, Laurent Debrauwer, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), 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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Metatoul AXIOM (E20 ), MetaboHUB-MetaToul, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Montréal (UdeM), This research was funded by the French National Infrastructure for metabolomics and fluxomics MetaboHUB ANR-11-INBS-010 and by the ExpoMycoPig project ANR-17-Carn012 and by an internal Toxalim grant., ANR-11-INBS-0010,METABOHUB,Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation(2011), LESUR, Hélène, Développement d'une infrastructure française distribuée pour la métabolomique dédiée à l'innovation - - METABOHUB2011 - ANR-11-INBS-0010 - INBS - VALID, Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), MetaToul-MetaboHUB, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse)
Subjects: Endocrinology, Diabetes and Metabolism, [SDV]Life Sciences [q-bio], Computational biology, Biology, Biochemistry, Microbiology, Article, Omics data, Transcriptome, 03 medical and health sciences, chemistry.chemical_compound, transcriptomics, 0302 clinical medicine, Metabolomics, statistical integration, Gene expression, mycotoxin exposure 1, metabolomics 3, mycotoxin exposure, Mycotoxin, Molecular Biology, Organism, 030304 developmental biology, 0303 health sciences, Phenotype, metabolomics, QR1-502, Metabolomics data, [SDV] Life Sciences [q-bio], chemistry, 030220 oncology & carcinogenesis, statistical integration 4, transcriptomics 2
Abstract: International audience; The effects of low doses of toxicants are often subtle and information extracted from metabolomic data alone may not always be sufficient. As end products of enzymatic reactions, metabolites represent the final phenotypic expression of an organism and can also reflect gene expression changes caused by this exposure. Therefore, the integration of metabolomic and transcriptomic data could improve the extracted biological knowledge on these toxicants induced disruptions. In the present study, we applied statistical integration tools to metabolomic and transcriptomic data obtained from jejunal explants of pigs exposed to the food contaminant, deoxynivalenol (DON). Canonical correlation analysis (CCA) and self-organizing map (SOM) were compared for the identification of correlated transcriptomic and metabolomic features, and O2-PLS was used to model the relationship between exposure and selected features. The integration of both ‘omics data increased the number of discriminant metabolites discovered (39) by about 10 times compared to the analysis of the metabolomic dataset alone (3). Besides the disturbance of energy metabolism previously reported, assessing correlations between both functional levels revealed several other types of damage linked to the intestinal exposure to DON, including the alteration of protein synthesis, oxidative stress, and inflammasome activation. This confirms the added value of integration to enrich the biological knowledge extracted from metabolomics
Published: 2021
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16. Toxicology of Mycotoxins: Overview and Challenges

Author: Nolwenn Hymery and Isabelle P. Oswald
Subjects: chemistry.chemical_compound, chemistry, business.industry, Biology, Mycotoxin, business, Biotechnology
Published: 2021
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17. The enteric nerve system as target of regulated and emerging food-associated mycotoxins

Author: Marc Maresca, Amine Kadri, Łukasz Zielonka, Isabelle P. Oswald, Michał Dąbrowski, Hamza Olleik, Philippe Pinton, and Valérie Camps
Subjects: Necrosis, Membrane permeability, Biology, In vitro, Microbiology, chemistry.chemical_compound, chemistry, Apoptosis, Toxicity, medicine, Cytotoxic T cell, medicine.symptom, Mycotoxin, Organism
Abstract: Food and feed are frequently contaminated by numerous regulated and emerging mycotoxins. Humans and animals are thus exposed daily to mycotoxins through the oral route making of the gut the first and the more exposed tissue. Although many studies have evaluated and demonstrated the impact of mycotoxins on the intestinal epithelial cells (IECs) and on the brain cells, surprisingly only few studies have investigated their impact on cells of the enteric nerve system (ENS). In the present work, we measured the impact of major regulated and emerging mycotoxins (17 mycotoxins in total) on the proliferation and viability of ENS cells in vitro. On the 17 mycotoxins tested, 9 were found active with anti-proliferative and cytotoxic effects observed at doses ranging from 0.19 to 16.4 µM and 0.4 to 38.4 µM, respectively. Mechanistic approaches revealed that toxicity on ENS cells was related to i) alteration of the membrane permeability, ii) ROS production and/or iii) induction of apoptosis/necrosis. Importantly, toxic doses found on ENS cells were compared to toxic doses found on IECs in order to determine if toxicity toward ENS was selective or not. Finally, toxic doses on ENS cells were compared to PMTDI and range of exposure in humans and animals in order to evaluate if ENS’s cells are a realistic target of food-associated mycotoxins and if alterations of ENS participate in the global impact of these toxins on the gut and the full organism.
Published: 2021
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18. Regulation of Secondary Metabolism in the Penicillium Genus

Author: Isabelle P. Oswald, Christelle El Hajj Assaf, Ali Atoui, Nadia Tahtah, Sophie Lorber, Olivier Puel, Chrystian Zetina-Serrano, André El Khoury, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), 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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Research Institute for Agricultural, Fisheries and Food (ILVO), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Saint-Joseph de Beyrouth (USJ), Faculty of Sciences [Lebanese University], Lebanese University [Beirut] (LU), International Cooperation Program CAPES/COFECUB (project number Sv 947/19), ANR-15-CE21-0010,Newmyco,Metabolome de deux contaminants fongiques du blé d'importance majeure: identification de nouveaux métabolites toxiques(2015), and ANR-17-CE21-0008,PATRISK,REDUCTION DU RISQUE PATULINE GRACE A UNE GESTION INTEGREE ET DURABLE DE LA PRODUCTION DE POMME ET DE PRODUITS DERIVES(2017)
Subjects: 0301 basic medicine, Ochratoxin A, animal structures, Range (biology), [SDV]Life Sciences [q-bio], 030106 microbiology, Biology, Catalysis, Inorganic Chemistry, Patulin, lcsh:Chemistry, 03 medical and health sciences, chemistry.chemical_compound, Human health, Genus, transcription factors, Botany, control of gene expression, Physical and Theoretical Chemistry, Secondary metabolism, Mycotoxin, Molecular Biology, lcsh:QH301-705.5, Spectroscopy, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, secondary metabolism, Organic Chemistry, Penicillium, food and beverages, regulation, General Medicine, 15. Life on land, biology.organism_classification, Computer Science Applications, virulence, 030104 developmental biology, chemistry, lcsh:Biology (General), lcsh:QD1-999, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; Penicillium, one of the most common fungi occurring in a diverse range of habitats, has a worldwide distribution and a large economic impact on human health. Hundreds of the species belonging to this genus cause disastrous decay in food crops and are able to produce a varied range of secondary metabolites, from which we can distinguish harmful mycotoxins. Some Penicillium species are considered to be important producers of patulin and ochratoxin A, two well-known mycotoxins. The production of these mycotoxins and other secondary metabolites is controlled and regulated by different mechanisms. The aim of this review is to highlight the different levels of regulation of secondary metabolites in the Penicillium genus.
Published: 2020
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19. Appropriateness to set a group health based guidance value for nivalenol and its modified forms

Author: EFSA Panel on Contaminants in the Food Chain (CONTAM), Helle Katrine Knutsen, Lars Barregård, Margherita Bignami, Beat Brüschweiler, Sandra Ceccatelli, Bruce Cottrill, Michael Dinovi, Lutz Edler, Bettina Grasl‐Kraupp, Christer Hogstrand, Laurentius (Ron) Hoogenboom, Carlo Stefano Nebbia, Isabelle P Oswald, Annette Petersen, Martin Rose, Alain‐Claude Roudot, Tanja Schwerdtle, Christiane Vleminckx, Günter Vollmer, Heather Wallace, Chiara Dall'Asta, Arno C Gutleb, Manfred Metzler, Dominique Parent‐Massin, Marco Binaglia, Hans Steinkellner, Jan Alexander, German Cancer Research Center, Division of Biostatistics, King‘s College London, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), ToxAlim (ToxAlim), 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), Institut National Polytechnique (Toulouse) (Toulouse INP), 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)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)
Subjects: 0301 basic medicine, Tolerable daily intake, Veterinary (miscellaneous), Metabolite, [SDV.TOX.TVM]Life Sciences [q-bio]/Toxicology/Vegetal toxicology and mycotoxicology, Physiology, TP1-1185, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, Plant Science, Body weight, 01 natural sciences, Microbiology, Toxicology, 03 medical and health sciences, chemistry.chemical_compound, biology.animal, group health based guidance value, Medicine, TX341-641, Mink, nivalenol, Reference dose, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Toxicity data, biology, Nutrition. Foods and food supply, business.industry, Chemical technology, 010401 analytical chemistry, modified forms, 3. Good health, 0104 chemical sciences, 030104 developmental biology, Scientific Opinion, chemistry, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Animal Science and Zoology, Parasitology, business, Food Science
Abstract: International audience; The EFSA Panel on Contaminants in the Food Chain (CONTAM) reviewed new studies on nivalenol since the previous opinion on nivalenol published in 2013, but as no new relevant data were identified the tolerable daily intake (TDI) for nivalenol (NIV) of 1.2 lg/kg body weight (bw) established on bases of immuno-and haematotoxicity in rats was retained. An acute reference dose (ARfD) of 14 lg/kg bw was established based on acute emetic events in mink. The only phase I metabolite of NIV identified is de-epoxy-nivalenol (DE-NIV) and the only phase II metabolite is nivalenol-3-glucoside (NIV3Glc). DE-NIV is devoid of toxic activity and was thus not further considered. NIV3Glc can occur in cereals amounting up to about 50% of NIV. There are no toxicity data on NIV3Glc, but as it can be assumed that it is hydrolysed to NIV in the intestinal tract it should be included in a group TDI and in a group ARfD with NIV. The uncertainty associated with the present assessment is considered as high and it would rather overestimate than underestimate any risk.
Published: 2020
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20. Dietary exposure to mycotoxins in the French infant total diet study

Author: Karine Vin, Jean Marc Fremy, Julien Jean, Paule Vasseur, Alain-Claude Roudot, Gilles Rivière, Véronique Sirot, Isabelle P. Oswald, Marion Hulin, Jean-Pierre Cravedi, Stéphane Leconte, Direction de l'Evaluation des Risques (DER), Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail (ANSES), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), 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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Retraité, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Brest (UBO), Laboratoire Interdisciplinaire des Environnements Continentaux (LIEC), Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Terre et Environnement de Lorraine (OTELo), Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut national des sciences de l'Univers (INSU - CNRS)-Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS)-Institut Ecologie et Environnement (INEE), and Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Ochratoxin A, Aflatoxin, MESH: Dietary Exposure, Context (language use), Food Contamination, MESH: Mycotoxins, Toxicology, MESH: Risk Assessment, Dietary exposure, Patulin, 03 medical and health sciences, chemistry.chemical_compound, 0404 agricultural biotechnology, Limit of Detection, Tandem Mass Spectrometry, Medicine, Humans, Mycotoxin, Zearalenone, Children, 030304 developmental biology, Risk assessment, 0303 health sciences, Diet study, business.industry, Infant, food and beverages, 04 agricultural and veterinary sciences, General Medicine, Mycotoxins, MESH: Food Contamination, 040401 food science, 3. Good health, chemistry, Child, Preschool, Total diet study, France, business, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science, Chromatography, Liquid
Abstract: International audience; The present study evaluated the exposure of children aged from one to 36 months to seven groups of mycotoxins, in the context of the infant French Total Diet Study (iTDS). Exposure was then compared to the health-based guidance values (HBGVs) for each mycotoxin. The value of the 90th percentile of exposure to nivalenol, patulin, fumonisins and zearalenone was less than 40% of the HBGV considered relevant for children. On the other hand, a risk could not be excluded for ochratoxin A and aflatoxins as exposure was close to the HBGV for ochratoxin A and the margin of exposure was much lower than the critical margin of 10,000 for aflatoxins. The HBGVs for toxins T2 and HT2, and for deoxynivalenol (DON) and its acetylated compounds were exceeded. Five percent to 10% of the children aged 5–12 months exceeded the HBGV considering the lower bound hypothesis for toxins T2 and HT2 and 7.5%–27% of the children aged 5 months and above exceeded the HBGV for DON. Consequently, the exposure of young children raises safety concerns for T2/HT2 and DON. Efforts should therefore be pursued to decrease their exposure to these molecules.
Published: 2020
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21. Proteome changes induced by a short, non-cytotoxic exposure to the mycoestrogen zearalenone in the pig intestine

Author: Alexandre Stella, Francisco J. Pallarés, Odile Burlet-Schiltz, Laura Soler, J. Seva, Tarek Lahjouji, Isabelle P. Oswald, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), 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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Universidad de Murcia, Department of Anatomy and Comparative Pathology, This project received funding from the European Union's Horizon 2020 research and innovation program under the Marie SklodowskaCurie grant agreement No. 722634 as well as by the Agence Nationale de la Recherche (ANR) grant ExpoMycoPig (ANR-17-Carn012). The work was also supported in part by the Region Occitanie, European funds (Fonds Europeens de Developpement Regional, FEDER), Toulouse Metropole, and the French Ministry of Research with the Investissement d'Avenir Infrastructures Nationales en Biologie et Sante program (ProFI, Proteomics French Infrastructure project, ANR-10-INBS-08)., and ANR-10-INBS-0008,ProFI,Infrastructure Française de Protéomique(2010)
Subjects: 0301 basic medicine, Proteomics, Chemokine, Proteome, Swine, Biophysics, Estrogen receptor, Estrogen receptors, Biology, medicine.disease_cause, Biochemistry, [SHS]Humanities and Social Sciences, 03 medical and health sciences, chemistry.chemical_compound, Immune system, medicine, Animals, CDX2, Pig, 030102 biochemistry & molecular biology, fungi, Mycoestrogen, Estrogens, Mycotoxins, 3. Good health, Cell biology, Intestine, Intestines, 030104 developmental biology, Endocrine disruptor, chemistry, biology.protein, Zearalenone, Signal transduction, Carcinogenesis, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; Intestinal epithelial homeostasis is regulated by a complex network of signaling pathways. Among them is es-trogen signaling, important for the proliferation and differentiation of epithelial cells, immune signaling andmetabolism. The mycotoxin zearalenone (ZEN) is an estrogen disruptor naturally found in food and feed. Theexposure of the intestine to ZEN has toxic effects including alteration of the immune status and is possiblyimplicated in carcinogenesis, but the molecular mechanisms linked with these effects are not clear. Our objectivewas to explore the proteome changes induced by a short, non-cytotoxic exposure to ZEN in the intestine using pigjejunal explants. Our results indicated that ZEN promotes little proteome changes, but significantly related withan induction of ERαsignaling and a consequent disruption of highly interrelated signaling cascades, such as NF-κB, ERK1/2, CDX2 and HIF1α. The toxicity of ZEN leads also to an altered immune status characterized by theactivation of the chemokine CXCR4/SDF-1 axis and an accumulation of MHC-I proteins. Our results connect theestrogen disrupting activity of ZEN with its intestinal toxic effect, associating the exposure to ZEN with cell-signaling disorders similar to those involved in the onset and progression of diseases such as cancer and chronicinflammatory disorders.Significance:The proteomics results presented in our study indicate that the endocrine disruptor activity of ZENis able to regulate a cascade of highly inter-connected signaling events essential for the small intestinal crypt-villus cycle and immune status. These molecular mechanisms are also implicated in the onset and progress ofintestinal immune disorders and cancer indicating that exposure to ZEN could play an important role in in-testinal pathogenesis
Published: 2020
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22. Mycotoxin mixtures in food and feed: holistic, innovative, flexible risk assessment modelling approach

Author: Roberta Palumbo, Rosaria Rosanna Cammarano, Chloé Terciolo, Paola Battilani, Ana Paula Monteiro Gonçalves, Carlo Brera, Isabelle P. Oswald, Nelson Lima, Piero Toscano, Athanasios Gkrillas, Maurella Della Seta, Paola Giorni, Katrina Campbell, Luca Dellafiora, Barbara De Santis, Alfonso Crisci, Christopher T. Elliot, Chiara Dall'Asta, Armando Venancio, and Universidade do Minho
Subjects: Biotecnologia Agrária e Alimentar [Ciências Agrárias], Ciências Agrárias::Biotecnologia Agrária e Alimentar, Avaliação de Risco, Biology, 01 natural sciences, Modelling, Mycotoxin co-occurrence, 03 medical and health sciences, chemistry.chemical_compound, Toxicokinetics, Mycotoxin, Risk assessment, 030304 developmental biology, 2. Zero hunger, Micotoxinas, 0303 health sciences, Toxicity, business.industry, 010401 analytical chemistry, Fungi, food and beverages, 0104 chemical sciences, Biotechnology, chemistry, 13. Climate action, business, Biomarkers
Abstract: Mycotoxins are toxic compounds mainly produced by fungi of the genera Aspergillus, Penicillium and Fusarium. They are present, often as mixtures, in many feed and food commodities including cereals, fruits and vegetables. Their ubiquitous presence represents a major challenge to the health and well being of humans and animals. Hundreds of compounds are listed as possible mycotoxins occurring in raw and processed materials destined for human food and animal feed. In this study, mycotoxins of major toxicological relevance to humans and target animal species were investigated in a range of crops of interest (and their derived products). Extensive Literature Searches (ELSs) were undertaken for data collection on: (i) ecology and interaction with host plants of mycotoxin producing fungi, mycotoxin production, recent developments in mitigation actions of mycotoxins in crop chains (maize, small grains, rice, sorghum, grapes, spices and nuts), (ii) analytical methods for native, modified and co-occurring mycotoxins (iii) toxicity, toxicokinetics, toxicodynamics and biomarkers relevant to humans and animals (poultry, suidae (pig, wild boar), bovidae (sheep, goat, cow, buffalo), rodents (rats, mice) and others (horses, dogs), (iv) modelling approaches and key reference values for exposure, hazard and risk modelling. Comprehensive databases were created using EFSA templates and were stored in the MYCHIF platform. A range of approaches were implemented to explore the modelling of external and internal exposure as well as dose-response of mycotoxins in chicken and pigs. In vitro toxicokinetic and in vivo toxicity databases were exploited, both for single compounds and mixtures. However, large data gaps were identified particularly with regards to absence of common statistical and study designs within the literature and constitute an obstacle for the harmonisation of internal exposure and dose-response modelling. Finally, risk characterisation was also performed for humans as well as for two animal species (i.e. pigs and chicken) using available tools for the modelling of internal dose and a component-based approach for selected mycotoxins mixtures.
Published: 2020
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23. 1H-NMR metabolomics response to a realistic diet contamination with the mycotoxin deoxynivalenol: Effect of probiotics supplementation

Author: Mathieu Castex, Marie Tremblay-Franco, Caroline Achard, Philippe Pinton, Ana Paula Frederico Rodrigues Loureiro Bracarense, Fabien Jourdan, Anne Marie Cossalter, Cécile Canlet, Imourana Alassane-Kpembi, Maxime Chalzaviel, Sylvie Combes, Isabelle P. Oswald, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), 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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université d'Abomey-Calavi, University of Abomey Calavi (UAC), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-ToxAlim (ToxAlim), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Métabolisme et Xénobiotiques (ToxAlim-MeX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), MedDay Pharmaceuticals, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Plateforme Ezop (Ezop), Lallemand S.A.S., Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Lab. Patologia Animal, and State University of Londrina = Universidade Estadual de Londrina
Subjects: pig, Biology, Toxicology, law.invention, histology, 03 medical and health sciences, chemistry.chemical_compound, Probiotic, 0404 agricultural biotechnology, Metabolomics, law, mycotoxins, Metabolome, Food science, Mycotoxin, intestine, 030304 developmental biology, Subclinical infection, 2. Zero hunger, 0303 health sciences, Saccharomyces cerevisiae boulardii, 04 agricultural and veterinary sciences, General Medicine, Metabolism, 040401 food science, metabolomics, Yeast, 3. Good health, chemistry, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Toxicity, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, Food Science
Abstract: International audience; Low-level contamination of food and feed by deoxynivalenol (DON) is unavoidable. We investigated the effects of subclinical treatment with DON, and supplementation with probiotic yeast Saccharomyces cerevisiae boulardii I1079 as a preventive strategy in piglets. Thirty-six animals were randomly assigned to either a control diet, a diet contaminated with DON (3 mg/kg), a diet supplemented with yeast (4 × 109 CFU/kg), or a DON-contaminated diet supplemented with yeast, for four weeks. Plasma and tissue samples were collected for biochemical analysis, 1H-NMR untargeted metabolomics, and histology. DON induced no significant modifications in biochemical parameters. However, lesion scores were higher and metabolomics highlighted alterations of amino acid and 2-oxocarboxylic acid metabolism. Administering yeast affected aminoacyl-tRNA synthesis and amino acid and glycerophospholipid metabolism. Yeast supplementation of piglets exposed to DON prevented histological alterations, and partial least square discriminant analysis emphasised similarity between the metabolic profiles of their plasma and that of the control group. The effect on liver metabolome remained marginal, indicating that the toxicity of the mycotoxin was not eliminated. These findings show that the 1H-NMR metabolomics profile is a reliable biomarker to assess subclinical exposure to DON, and that supplementation with S. cerevisiae boulardii increases the resilience of piglets to this mycotoxin.
Published: 2020
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24. An in silico structural approach to characterize human and rainbow trout estrogenicity of mycotoxins: Proof of concept study using zearalenone and alternariol

Author: Gianni Galaverna, Isabelle P. Oswald, Paola Battilani, Jean-Lou Dorne, Chiara Dall'Asta, Luca Dellafiora, University of Parma = Università degli studi di Parma [Parme, Italie], ToxAlim (ToxAlim), 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), Institut National Polytechnique (Toulouse) (Toulouse INP), 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), European Food Safety Authority (EFSA), and Università cattolica del Sacro Cuore [Piacenza e Cremona] (Unicatt)
Subjects: Toxicodynamics, Estrone, In silico, Alternariol, toxicodynamic, Estrogen receptors, In silico toxicology, Mycotoxins, Toxicodynamic, Zearalenone, Computational biology, in silico toxicology, Proof of Concept Study, 01 natural sciences, alternariol, Analytical Chemistry, Lactones, chemistry.chemical_compound, 0404 agricultural biotechnology, mycotoxins, Animals, Humans, Computer Simulation, Mycotoxin, [SDV.MP.MYC]Life Sciences [q-bio]/Microbiology and Parasitology/Mycology, Molecular Structure, biology, 010401 analytical chemistry, zearalenone, estrogen receptors, 04 agricultural and veterinary sciences, General Medicine, biology.organism_classification, 040401 food science, 0104 chemical sciences, Trout, chemistry, Oncorhynchus mykiss, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Rainbow trout, Pharmacophore, Settore AGR/12 - PATOLOGIA VEGETALE, Food Science
Abstract: International audience; The mycotoxins zearalenone and alternariol may contaminate food and feed raising toxicological concerns due to their estrogenicity. Inter-species differences in their toxicokinetics and toxicodynamics may occur depending on evolution of taxa-specific traits. As a proof of principle, this manuscript investigates the comparative toxicodynamics of zearalenone, its metabolites (alpha-zearalenol and beta-zearalenol), and alternariol with regards to estrogenicity in humans and rainbow trout. An in silico structural approach based on docking simulations, pharmacophore modeling and molecular dynamics was applied and computational results were analyzed in comparison with available experimental data. The differences of estrogenicity among species of zearalenone and its metabolites have been structurally explained. Also, the low estrogenicity of alternariol in trout has been characterized here for the first time. This approach can provide a powerful tool for the characterization of interspecies differences in mycotoxin toxicity for a range of protein targets and relevant compounds for the food- and feed-safety area.
Published: 2020
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25. Individual tree and stand-level carbon and nutrient contents across one rotation of loblolly pine plantations on a reclaimed surface mine

Author: Yuhui Weng, Hans M. Williams, Hannah Z. Angel, Jeremy P. Stovall, Brian P. Oswald, and Jeremy S. Priest
Subjects: 0106 biological sciences, geography, geography.geographical_feature_category, Coastal plain, Phosphorus, Chronosequence, chemistry.chemical_element, Reforestation, Forestry, 04 agricultural and veterinary sciences, Site index, 01 natural sciences, Nutrient, chemistry, Agronomy, Productivity (ecology), 040103 agronomy & agriculture, 0401 agriculture, forestry, and fisheries, Environmental science, Cycling, 010606 plant biology & botany
Abstract: While reclaimed loblolly pine (Pinus taeda L.) plantations in east Texas, USA have demonstrated similar aboveground productivity levels relative to unmined forests, there is interest in assessing carbon (C) and nutrients in aboveground components of reclaimed trees. Numerous studies have previously documented aboveground biomass, C, and nutrient contents in loblolly pine plantations; however, similar data have not been collected on mined lands. We investigated C, N, P, K, Ca, and Mg aboveground contents for first-rotation loblolly pine growing on reclaimed mined lands in the Gulf Coastal Plain over a 32-year chronosequence and correlated elemental rates to stand age, stem growth, and similar data for unmined lands. At the individual tree level, we evaluated elemental contents in aboveground biomass components using tree size, age, and site index as predictor variables. At the stand-level, we then scaled individual tree C and nutrients and fit a model to determine the sensitivity of aboveground elemental contents to stand age and site index. Our data suggest that aboveground C and nutrients in loblolly pine on mined lands exceed or follow similar trends to data for unmined pine plantations derived from the literature. Diameter and height were the best predictors of individual tree stem C and nutrient contents (R ≥ 0.9473 and 0.9280, respectively) followed by stand age (R ≥ 0.8660). Foliage produced weaker relationships across all predictor variables compared to stem, though still significant (P ≤ 0.05). The model for estimating stand-level C and nutrients using stand age provided a good fit, indicating that contents aggrade over time predictably. Results of this study show successful modelling of reclaimed loblolly pine aboveground C and nutrients, and suggest elemental cycling is comparable to unmined lands, thus providing applicability of our model to related systems.
Published: 2018
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26. Cobalt-Catalyzed Oxygenation/Dearomatization of Furans

Author: K. A. Woerpel and Jonathan P. Oswald
Subjects: Silylation, 010405 organic chemistry, Organic Chemistry, chemistry.chemical_element, Cobalt, Oxygenation, 010402 general chemistry, 01 natural sciences, Article, Catalysis, 0104 chemical sciences, Oxygen, chemistry.chemical_compound, chemistry, Triplet oxygen, Organic chemistry, Triethylsilane, Furans
Abstract: The dearomatization of aromatic compounds using cobalt(II) acetylacetonate with triplet oxygen and triethylsilane converts furans, benzofurans, pyrroles, and thiophenes to a variety of products, including lactones, silyl peroxides, and ketones.
Published: 2018
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27. Impact ofveAon the development, aggressiveness, dissemination and secondary metabolism ofPenicillium expansum

Author: Claire Naylies, Isabelle P. Oswald, Olivier Puel, Sophie Lorber, Christelle El Hajj Assaf, Sylviane Bailly, Souria Tadrist, and Selma P. Snini
Subjects: 2. Zero hunger, 0301 basic medicine, biology, food and beverages, Soil Science, Plant Science, biology.organism_classification, Microbiology, Patulin, Citrinin, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, Biosynthesis, chemistry, Gene expression, Penicillium expansum, Secondary metabolism, Agronomy and Crop Science, Molecular Biology, Gene, Transcription factor
Abstract: Penicillium expansum, the causal agent of blue mould disease, produces the mycotoxins patulin and citrinin amongst other secondary metabolites. Secondary metabolism is associated with fungal development, which responds to numerous biotic and abiotic external triggers. The global transcription factor VeA plays a key role in the coordination of secondary metabolism and differentiation processes in many fungal species. The specific role of VeA in P. expansum remains unknown. A null mutant PeΔveA strain and a complemented PeΔveA:veA strain were generated in P. expansum and their pathogenicity on apples was studied. Like the wild‐type and the complemented strains, the null mutant PeΔveA strain was still able to sporulate and to colonize apples, but at a lower rate. However, it could not form coremia either in vitro or in vivo, thus limiting its dissemination from natural substrates. The impact of veA on the expression of genes encoding proteins involved in the production of patulin, citrinin and other secondary metabolites was evaluated. The disruption of veA drastically reduced the production of patulin and citrinin on synthetic media, associated with a marked down‐regulation of all genes involved in the biosynthesis of the two mycotoxins. Moreover, the null mutant PeΔveA strain was unable to produce patulin on apples. The analysis of gene expression revealed a global impact on secondary metabolism, as 15 of 35 backbone genes showed differential regulation on two different media. These findings support the hypothesis that VeA contributes to the pathogenicity of P. expansum and modulates its secondary metabolism.
Published: 2018
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28. 1H NMR and MVA metabolomic profiles of urines from piglets fed with boluses contaminated with a mixture of five mycotoxins

Author: Isabelle P. Oswald, Francesco Paolo Fanizzi, Lucia Gambacorta, Laura Del Coco, Michele Solfrizzo, Sandra Angelica De Pascali, Di.S.Te.B.A., Università del Salento, Institute of Sciences of Food Production (ISPA), Consiglio Nazionale delle Ricerche (CNR), ToxAlim (ToxAlim), 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), Institut National Polytechnique (Toulouse) (Toulouse INP), 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), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), De Pascali, Sandra A., Gambacorta, Lucia, Oswald, Isabelle P., Del Coco, Laura, Solfrizzo, Michele, and Fanizzi, Francesco Paolo
Subjects: 0301 basic medicine, Ochratoxin A, mycotoxine, Animal feed, [SDV]Life Sciences [q-bio], Biophysics, toxicologie alimentaire, chimiométrie, Chemometric, Metabolomic, Urine, human health, Biochemistry, lcsh:Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, 0404 agricultural biotechnology, Betaine, Fumonisin, Metabolomics, lcsh:QD415-436, Chemometrics, Mycotoxin, 1H NMR spectroscopy, Molecular Biology, Zearalenone, lcsh:QH301-705.5, Chromatography, H NMR spectroscopy, food and beverages, Cell Biology, 04 agricultural and veterinary sciences, santé humaine, Biomarker, 040401 food science, 3. Good health, 030104 developmental biology, Biophysic, chemistry, spectroscopie résonance magnétique nucléaire, lcsh:Biology (General), Glucuronide, biomarqueur, métabolomique, Research Article
Abstract: Metabolic profile of urine from piglets administered with single boluses contaminated with mycotoxin mixture (deoxynivalenol, aflatoxin B1, fumonisin B1, zearalenone, and ochratoxin A) were studied by 1H NMR spectroscopy and chemometrics (PCA, PLS-DA, and OPLS-DA). The mycotoxin levels were close to the established maximum and guidance levels for animal feed (2003/100/EC and 2006/576/EC). Urine samples were obtained from four groups of four piglets before (control, C) or within 24 h (treated, T) after receiving a contaminated boluses with increasing doses of mycotoxins (boluses 1–4). For the two highest dose groups, the urines were collected also after one week of wash out (W). For the two lowest doses groups no significant differences between the C and T samples were observed. By contrast, for the two highest doses groups the T urines separated from the controls for a higher relative content of creatinine, p-cresol glucuronide and phenyl acetyl glycine and lower concentration of betaine and TMAO. Interestingly, a similar profile was found for both W and T urines suggesting, at least for the highest doses used, serious alteration after a single bolus of mycotoxin mixture., Highlights • A single dose of mycotoxins mixture (DON, AFB1, FB1, ZEN, and OTA ) could produce serious impairments of gut microbiota of piglets. • The explorative metabolomic analysis on urine piglets, fed with boluses contaminated with mycotoxins mixtures, was performed. • NMR-based MVA resulted in a higher urinary concentrations of creatinine, p-cresol glucuronide and phenyl acetyl glycine and lower concentrations of betaine and TMAO after treatment with respect to own controls.
Published: 2017
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29. Reduced toxicity of 3-epi-deoxynivalenol and de-epoxy-deoxynivalenol through deoxynivalenol bacterial biotransformation

Author: Wulf-Dieter Moll, Ana Paula Frederico Rodrigues Loureiro Bracarense, Juliana Rubira Gerez, Gerd Schatzmayr, Philippe Pinton, Isabelle P. Oswald, Ting Zhou, Alix Pierron, Laboratory of Animal Pathology, State University of Londrina = Universidade Estadual de Londrina, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), 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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), BIOMIN Research Center, Agriculture and Agri-Food [Ottawa] (AAFC), This work was partially financed by the Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES), Brazil and Comite Frances de Avaliacao da Cooperacao Universitaria com o Brasil (COFECUB), France, CAPES/COFECUB Program (number 0389/2019) and Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Brazil (number 308136/2018-7)., Biomin Research Center, Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Brazil, Comitê Francês de Avaliação da Cooperação Universitária com o Brasil (COFECUB), CAPES/COFECUB Program (number 0389/2019), and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil (number 308136/2018-7)
Subjects: Male, medicine.medical_specialty, Lymphoid Tissue, Swine, [SDV]Life Sciences [q-bio], [SDV.TOX.TVM]Life Sciences [q-bio]/Toxicology/Vegetal toxicology and mycotoxicology, Histopathology, Immunoglobulins, Food Contamination, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, Biology, Toxicology, Occludin, Weight Gain, Microbiology, Immunomodulation, 03 medical and health sciences, chemistry.chemical_compound, 0404 agricultural biotechnology, Biotransformation, Detoxification, Intestine, Small, medicine, Ingestion, Animals, Mycotoxin, Adverse effect, 030304 developmental biology, 2. Zero hunger, 0303 health sciences, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, food and beverages, 04 agricultural and veterinary sciences, General Medicine, Organ Size, Mycotoxins, 040401 food science, Animal Feed, 3. Good health, chemistry, Liver, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Toxicity, Cytokines, Trichothecenes, Food Science
Abstract: International audience; Ingestion of deoxynivalenol (DON), one of the most common mycotoxin contaminants of cereals, leads to adverse effects for animal and human health. Bacterial biotransformation is a strategy to mitigate the toxicity of this mycotoxin. The present study aims to evaluate the toxicity of two bacterial biotranformation products of DON: 3-epi-deoxynivalenol (3-epi-DON) and de-epoxy-deoxynivalenol (DOM-1) through zootechnical, hematological, histological and immunological assays. Twenty-four 4weeks-old piglets received a control diet or a diet contaminated with 3 mg kg-1 DON, DOM-1, or 3-epi-DON for 7 days. Sample tissues were collected for histomorphometrical analysis, expression of cytokines and cell protein junctions. The zootechnical and hematological parameters were not modulated by any treatment. Ingestion of DON induced histological alterations in the intestine, liver and lymphoid organs, as well as an overexpression of pro-inflammatory cytokines, E-cadherin and occludin. These changes were not observed in piglets receiving the DOM-1 and 3-epi-DON contaminated diets. Pigs fed 3-epi-DON contaminated diet showed an increase in IgM levels in comparison with other diets, while no change was observed in IgA and IgG levels among the diets. Our results indicate that DOM-1 and 3-epi-DON are not toxic for piglets; thus bacterial biotransformation seems to be a sustainable alternative to reduce mycotoxin toxicity.
Published: 2019
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30. Aflatoxin Biosynthesis and Genetic Regulation: A Review

Author: Isabelle P. Oswald, Anthony Al Khoury, André El Khoury, Sophie Lorber, Isaura Caceres, Ali Atoui, Jean-Denis Bailly, Rhoda El Khoury, Olivier Puel, ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), 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 Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Saint-Joseph de Beyrouth (USJ), Lebanese University [Beirut] (LU), and Bailly, Jean-Denis
Subjects: Aflatoxin, [SDV]Life Sciences [q-bio], Health, Toxicology and Mutagenesis, lcsh:Medicine, Aspergillus flavus, Fungus, Review, Aspergillus, aflatoxin, biosynthesis, gene regulation, Toxicology, aspergillus, 03 medical and health sciences, chemistry.chemical_compound, Aflatoxins, Animals, Humans, Gene, 030304 developmental biology, 2. Zero hunger, Genetics, Regulation of gene expression, 0303 health sciences, biology, 030306 microbiology, business.industry, lcsh:R, biology.organism_classification, Food safety, chemistry, Gene-Environment Interaction, business, Sterigmatocystin
Abstract: International audience; The study of fungal species evolved radically with the development of molecular techniques and produced new evidence to understand specific fungal mechanisms such as the production of toxic secondary metabolites. Taking advantage of these technologies to improve food safety, the molecular study of toxinogenic species can help elucidate the mechanisms underlying toxin production and enable the development of new effective strategies to control fungal toxicity. Numerous studies have been made on genes involved in aflatoxin B1 (AFB1) production, one of the most hazardous carcinogenic toxins for humans and animals. The current review presents the roles of these different genes and their possible impact on AFB1 production. We focus on the toxinogenic strains Aspergillus flavus and A. parasiticus, primary contaminants and major producers of AFB1 in crops. However, genetic reports on A. nidulans are also included because of the capacity of this fungus to produce sterigmatocystin, the penultimate stable metabolite during AFB1 production. The aim of this review is to provide a general overview of the AFB1 enzymatic biosynthesis pathway and its link with the genes belonging to the AFB1 cluster. It also aims to illustrate the role of global environmental factors on aflatoxin production and the recent data that demonstrate an interconnection between genes regulated by these environmental signals and aflatoxin biosynthetic pathway.
Published: 2019
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31. Cobalt-Catalyzed Intramolecular Silylperoxidation of Unsaturated Diisopropylsilyl Ethers

Author: Jonathan P. Oswald and K. A. Woerpel
Subjects: Silicon, Extramural, Organic Chemistry, chemistry.chemical_element, Cobalt, Ring (chemistry), Medicinal chemistry, Peroxide, Catalysis, Article, Peroxides, chemistry.chemical_compound, chemistry, Intramolecular force, Ethers
Abstract: A cobalt-catalyzed intramolecular silylperoxidation reaction was developed that allows for the conversion of unsaturated diisopropylsilyl ethers to 3-sila-1,2,4-trioxepanes. Reduction of the peroxide unit of the 3-sila-1,2,4-trioxepane yields six-membered ring diisopropylsilylene acetals.
Published: 2019

32. Deoxynivalenol inhibits the expression of trefoil factors (TFF) by intestinal human and porcine goblet cells

Author: Mehdi Sicre, Philippe Pinton, Ange Pujol, Cendrine Nicoletti, Fabien Graziani, Nathalie Quinson, Josette Perrier, Eric Di Pasquale, Marc Maresca, Isabelle P. Oswald, El Hassan Ajandouz, Hamza Olleik, Institut des Sciences Moléculaires de Marseille (ISM2), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), ToxAlim (ToxAlim), 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), Institut National Polytechnique (Toulouse) (Toulouse INP), 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)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Laboratoire de Neurosciences Cognitives [Marseille] (LNC), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Institut de neurophysiopathologie (INP), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Aix Marseille Université (AMU)-École Centrale de Marseille (ECM)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), 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), 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)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0301 basic medicine, MAPK/ERK pathway, Trefoil Factors, Cell Survival, Swine, Health, Toxicology and Mutagenesis, p38 mitogen-activated protein kinases, [SDV]Life Sciences [q-bio], Cell Culture Techniques, Gene Expression, Inflammation, 010501 environmental sciences, Toxicology, 01 natural sciences, 03 medical and health sciences, TFF3, Cell Movement, medicine, Animals, Humans, Secretion, Barrier function, TFF2, 0105 earth and related environmental sciences, Goblet cells, TFF1, Mycotoxin, Chemistry, Kinase, General Medicine, Deoxynivalenol, 3. Good health, Cell biology, Jejunum, 030104 developmental biology, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Caco-2 Cells, Trefoil Factor-3, medicine.symptom, Trichothecenes, Wound healing, HT29 Cells
Abstract: International audience; Trefoil factors (TFFs) are bioactive peptides expressed by several epithelia, including the intestine, where they regulate key functions such as tissue regeneration, barrier function and inflammation. Although food-associated mycotoxins, including deoxynivalenol (DON), are known to impact many intestinal functions, modulation of TFFs during mycotoxicosis has never been investigated. Here, we analyzed the effect of DON on TFFs expression using both human goblet cells (HT29-16E cells) and porcine intestinal explants. Results showed that very low doses of DON (nanomolar range) inhibit the secretion of TFFs by human goblet cells (IC50 of 361, 387 and 243 nM for TFF1, 2 and 3, respectively) and prevent wound healing. RT-qPCR analysis demonstrated that the inhibitory effect of DON is related to a suppression of TFFs mRNA expression. Experiments conducted on porcine intestinal explants confirmed the results obtained on cells. Finally, the use of specific inhibitors of signal pathways demonstrated that DON-mediated suppression of TFFs expression mainly involved Protein Kinase R and the MAP kinases (MAPK) p38 and ERK1/2. Taken together, our results show for the first time that at very low doses, DON suppresses the expression and production of intestinal TFFs and alters wound healing. Given the critical role of TFFs in tissue repair, our results suggest that DON-mediated suppression of TFFs contributes to the alterations of intestinal integrity the caused by this toxin.
Published: 2019
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33. Combined hazard assessment of mycotoxins and their modified forms applying relative potency factors

Author: Marco Binaglia, Chiara Dall'Asta, Arno C. Gutleb, Manfred Metzler, Dominique Parent-Massin, Hans Steinkellner, Jan Alexander, Isabelle P. Oswald, European Food Safety Authority (EFSA), Department of Food and Drug, University of Parma = Università degli studi di Parma [Parme, Italie], Environmental Research and Innovation (ERIN) Department, Luxembourg Institute of Science and Technology (LIST), Institute of Applied Biosciences, Karlsruhe Institute of Technology (KIT), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), ToxAlim (ToxAlim), 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), Institut National Polytechnique (Toulouse) (Toulouse INP), 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)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Université de Bretagne Occidentale, Norwegian institute for public health, Université de Bretagne Occidentale - UFR Sciences et Techniques (UBO UFR ST), Université de Brest (UBO), and Norwegian Institute of Public Health [Oslo] (NIPH)
Subjects: Tolerable daily intake, [SDV.TOX.TVM]Life Sciences [q-bio]/Toxicology/Vegetal toxicology and mycotoxicology, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, Pharmacology, Toxicology, medicine.disease_cause, Risk Assessment, 03 medical and health sciences, chemistry.chemical_compound, Ttoxicity assessment, relative potency factors (RPFs), 0404 agricultural biotechnology, In vivo, medicine, T2-toxin (HT2), Potency, toxicity assessment, Animals, Humans, Mycotoxin, Mode of action, Zearalenone, 030304 developmental biology, 0303 health sciences, Reference dose, No-Observed-Adverse-Effect Level, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Chemistry, Toxin, fungi, modified forms, zearalenone (ZEN), Estrogens, 04 agricultural and veterinary sciences, General Medicine, 040401 food science, 3. Good health, T-2 Toxin, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Food Science
Abstract: International audience; This paper describes a methodology for hazard assessment of groups of related substances for which toxicity data are insufficient, and which utilises, next to conventional toxicological assessments and mechanistic information, the derivation of relative toxicity potency factors (RPFs). Zearalenone (ZEN) and T-2 toxin (T2) and HT-2 toxin (HT2) and their modified forms have been used as examples. A tolerable daily intake (TDI) for ZEN of 0.25 µg/kg bw was established. In vitro and in vivo studies suggested that modified forms of ZEN act via the same mode of action as ZEN (oestrogenicity). Results from in vivo uterotrophic assays were used to establish RPFs, allowing inclusion the different modified forms in a group TDI with ZEN. A TDI for the sum of T2/HT2 of 0.02 µg/kg bw per day and an acute reference dose (ARfD) of 0.3 µg/kg bw for the sum of T2/HT2 was established. In vitro studies show that phase I metabolites of T2/HT2 act via a similar mode of action as their parent compounds, namely protein synthesis inhibition with immune-and haematotoxicity. The phase I *Manuscript for revision (track changes hidden) Click here to view linked References 2 metabolites as well as conjugates of T2/HT2 and their phase I metabolites can be included in a group TDI with T2/HT2 applying RPFs.
Published: 2019
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34. Co-occurrence of DON and emerging mycotoxins in worldwide finished pig feed and their combined toxicity in intestinal cells

Author: Barbara Novak, Abdullah Khan Khoshal, Isabelle P. Oswald, Gerd Schatzmayr, Timothy P. Jenkins, Manon Neves, Philippe Pinton, Pascal G.P. Martin, ToxAlim (ToxAlim), 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), Institut National Polytechnique (Toulouse) (Toulouse INP), 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), BIOMIN Research Center, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and Pinton, Philippe
Subjects: Fusarium, IPEC-1, Cell Survival, Swine, Health, Toxicology and Mutagenesis, emerging mycotoxins, global survey, Food Contamination, Toxicology, 01 natural sciences, DON, co-occurrence, combined toxicitty, finished pig feed, toxicity, Article, Cell Line, 03 medical and health sciences, chemistry.chemical_compound, Animals, Food science, Mycotoxin, Toxicologie, 030304 developmental biology, 0303 health sciences, biology, 010401 analytical chemistry, Brevianamide F, food and beverages, Epithelial Cells, Mycotoxins, biology.organism_classification, Animal Feed, Beauvericin, 0104 chemical sciences, 3. Good health, Intestines, chemistry, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Penicillium, Toxicity, Emodin, combined toxicity, Enniatin
Abstract: Food and feed can be naturally contaminated by several mycotoxins, and concern about the hazard of exposure to mycotoxin mixtures is increasing. In this study, more than 800 metabolites were analyzed in 524 finished pig feed samples collected worldwide. Eighty-eight percent of the samples were co-contaminated with deoxynivalenol (DON) and other regulated/emerging mycotoxins. The Top 60 emerging/regulated mycotoxins co-occurring with DON in pig feed shows that 48%, 13%, 8% and 12% are produced by Fusarium, Aspergillus, Penicillium and Alternaria species, respectively. Then, the individual and combined toxicity of DON and the 10 most prevalent emerging mycotoxins (brevianamide F, cyclo-(L-Pro-L-Tyr), tryptophol, enniatins A1, B, B1, emodin, aurofusarin, beauvericin and apicidin) was measured at three ratios corresponding to pig feed contamination. Toxicity was assessed by measuring the viability of intestinal porcine epithelial cells, IPEC-1, at 48-h. BRV-F, Cyclo and TRPT did not alter cell viability. The other metabolites were ranked in the following order of toxicity: apicidin &gt, enniatin A1 &gt, DON &gt, beauvericin &gt, enniatin B &gt, enniatin B1 &gt, emodin &gt, aurofusarin. In most of the mixtures, combined toxicity was similar to the toxicity of DON alone. In terms of pig health, these results demonstrate that the co-occurrence of emerging mycotoxins that we tested with DON does not exacerbate toxicity.
Published: 2019
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35. Combination of isotope labeling and molecular networking of tandem mass spectrometry data to reveal 69 unknown metabolites produced by Penicillium nordicum

Author: Thaïs Hautbergue, Jean-Claude Tabet, Olivier Puel, Robin Costantino, Laurent Debrauwer, Isabelle P. Oswald, Emilien L. Jamin, Souria Tadrist, Lauriane Meneghetti, ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut Parisien de Chimie Moléculaire (IPCM), Chimie Moléculaire de Paris Centre (FR 2769), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Centre National de la Recherche Scientifique (CNRS)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Institut National de la Recherche Agronomique (INRA), French Minister of Higher Education and Research, French National Agency of Research French National Research Agency (ANR) [Newmyco-ANR-15-CE21-0010-21], Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), 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), MetaToul AXIOM (E20), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Ecole Nationale Supérieure de Chimie de Paris - Chimie ParisTech-PSL (ENSCP), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Paris (ENS-PSL), Université Paris sciences et lettres (PSL)-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), 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), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-MetaToul-MetaboHUB, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris), and Université Paris sciences et lettres (PSL)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut de Chimie du CNRS (INC)-École normale supérieure - Paris (ENS Paris)
Subjects: 2. Zero hunger, molecular networking, Chromatography, labeled fungal cultures, secondary metabolites, unambigous formulas, 010401 analytical chemistry, structure elucidation, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, 010402 general chemistry, Tandem mass spectrometry, Mass spectrometry, 01 natural sciences, Isotopes of nitrogen, 0104 chemical sciences, Analytical Chemistry, chemistry.chemical_compound, Metabolomics, chemistry, Metabolome, Penicillium nordicum, Secondary metabolism, Ochratoxin, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; The secondary metabolome of Penicillium nordicum is poorly documented despite its frequent detection on contaminated food and its capacity to produce toxic metabolites such as ochratoxin A. To characterize metabolites produced by this fungi, we combined a full stable isotopes labeling with the dereplication of tandem mass spectrometry (MS/MS) data by molecular networking. First, the untargeted metabolomic analysis by high-resolution mass spectrometry of a double stable isotope labeling of P. nordicum enabled the specific detection of its metabolites and the unambiguous determination of their elemental composition. Analyses showed that infection of substrate by P. nordicum lead to the production of at least 92 metabolites and that 69 of them were completely unknown. Then, curated molecular networks of MS/MS data were generated with GNPS and MetGem, specifically on the features of interest, which allowed highlighting 13 fungisporin-related metabolites that had not previously been identified in this fungus and 8 that had never been observed in any fungus. The structures of the unknown compounds, namely, a native fungisporin and seven linear peptides, were characterized by tandem mass spectrometry experiments. The analysis of P. nordicum growing on its natural substrates, i.e. pork ham, turkey ham, and cheese, demonstrated that 10 of the known fungisporin-related metabolites and three of the new metabolites were also synthesized. Thus, the curation of data for molecular networking using a specific detection of metabolites of interest with stable isotopes labeling allowed the discovery of new metabolites produced by the food contaminant P. nordicum.
Published: 2019
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36. Patulin transformation products and last intermediates in its biosynthetic pathway, E- and Z-ascladiol, are not toxic to human cells

Author: Joanna Tannous, Isabelle P. Oswald, Thierry Gauthier, Rhoda El Khoury, Cécile Canlet, Philippe Pinton, Selma P. Snini, Ali Atoui, André El Khoury, Ting Zhou, Roger Lteif, Yannick Lippi, Olivier Puel, Imourana Alassane-Kpembi, ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Faculté des Sciences, Centre d’Analyses et de Recherches, Université Saint-Joseph de Beyrouth (USJ), Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Transcriptomic impact of Xenobiotics (E23 TRiX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Plateforme Génome & Transcriptome (GET), Contaminants & Stress Cellulaire (ToxAlim-COMICS), Lebanese Atomic Energy Commission, Centre National de la Recherche Scientifique (CNRS), Faculty of Sciences, Laboratory of Microbiology, Department of Biology, Lebanese University [Beirut] (LU), Guelph Research and Development Center, Agriculture and Agri-Food [Ottawa] (AAFC), project CASDAR AAP RT 2015 No. 1523, 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), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-MetaToul-MetaboHUB, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Plateforme Génome & Transcriptome (GET), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Lebanese University [Beirut]
Subjects: 0301 basic medicine, penicillium expansum, Cell Survival, [SDV]Life Sciences [q-bio], Health, Toxicology and Mutagenesis, Genes, Fungal, 030106 microbiology, Mutant, toxicologie alimentaire, HL-60 Cells, Biology, Toxicology, Patulin, 03 medical and health sciences, chemistry.chemical_compound, Isomerism, Humans, Furans, Cytotoxicity, Mycotoxin, Dose-Response Relationship, Drug, ATP synthase, Microarray analysis techniques, Penicillium, patulin synthase, patuline, Hep G2 Cells, General Medicine, biology.organism_classification, patE gene, HEK293 Cells, 030104 developmental biology, chemistry, Biochemistry, Organ Specificity, Cell culture, biology.protein, cytotoxicity, microarray analysis, Caco-2 Cells, Penicillium expansum, ascladiol, Gene Deletion
Abstract: Patulin is the main mycotoxin contaminating apples. During the brewing of alcoholic beverages, this mycotoxin is degraded to ascladiol, which is also the last precursor of patulin. The present study aims (1) to characterize the last step of the patulin biosynthetic pathway and (2) to describe the toxicity of ascladiol. A patE deletion mutant was generated in Penicillium expansum. In contrast to the wild strain, this mutant does not produce patulin but accumulates high levels of E-ascladiol with few traces of Z-ascladiol. This confirms that patE encodes the patulin synthase involved in the conversion of E-ascladiol to patulin. After purification, cytotoxicities of patulin and E- and Z-ascladiol were investigated on human cell lines from liver, kidney, intestine, and immune system. Patulin was cytotoxic for these four cell lines in a dose-dependent manner. By contrast, both E- and Z-ascladiol were devoid of cytotoxicity. Microarray analyses on human intestinal cells treated with patulin and E-ascladiol showed that the latter, unlike patulin, did not alter the whole human transcription. These results demonstrate that E- and Z-ascladiol are not toxic and therefore patulin detoxification strategies leading to the accumulation of ascladiol are good approaches to limit the patulin risk.
Published: 2016
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37. The protective role of liver X receptor (LXR) during fumonisin B1-induced hepatotoxicity

Author: Marion Régnier, Talal Al Saati, Sarra Smati, Arnaud Polizzi, Yannick Lippi, Colette Bétoulières, Joëlle Laffitte, Hervé Guillou, Hester Mari Burger, Simon Ducheix, Frédéric Lasserre, Alexandra Montagner, Pascal Gourbeyre, Claire Naylies, Justine Bertrand-Michel, Sandrine Ménard, Isabelle P. Oswald, Nicolas Loiseau, Céline Lukowicz, Wentzel C. A. Gelderblom, Jean-Marc A. Lobaccaro, Sandrine Ellero-Simatos, ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Toxicologie Intégrative & Métabolisme (ToxAlim-TIM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Institut National de la Santé et de la Recherche Médicale (INSERM), Transcriptomic impact of Xenobiotics (E23 TRiX), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Plateforme Génome & Transcriptome (GET), Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Plateforme Ezop (Ezop), Neuro-Gastroentérologie & Nutrition (ToxAlim-NGN), Génétique, Reproduction et Développement (GReD), Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM), Cape Peninsula University of Technology (CPUT), Department of Biochemistry, Hôpital Lapeyronie, Ministere de l'Education Nationale, de la Recherche et de la Technologie, ANR Fumolip [ANR-16-CE21-0003], ANR LipoReg, France [ANR-15-Carn0016], Université de Toulouse (UT)-Université de Toulouse (UT)-Ecole Nationale Vétérinaire de Toulouse (ENVT), 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)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Institut des Maladies Métaboliques et Casdiovasculaires (UPS/Inserm U1297 - I2MC), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), MetaboHUB-MetaToul, MetaboHUB-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Centre Régional d'Exploration Fonctionnelle et Ressources Expérimentales (CREFRE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Clermont Auvergne (UCA), Stellenbosch University, ANR-16-CE21-0003,Fumolip,Toxicité d'un contaminant alimentaire majeur, la fumonisine: rôle du métabolisme lipidique et stratégie nutritionnelle de détoxication(2016), 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), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Plateforme Génome & Transcriptome (GET), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)
Subjects: 0301 basic medicine, medicine.drug_class, Health, Toxicology and Mutagenesis, 010501 environmental sciences, Pharmacology, Toxicology, 01 natural sciences, digestive system, Fumonisins, Intestinal absorption, Nephrotoxicity, Transaminase, Ceramide, 03 medical and health sciences, chemistry.chemical_compound, medicine, Animals, Aspartate Aminotransferases, Liver X receptor, 0105 earth and related environmental sciences, Liver X Receptors, Mice, Knockout, Fumonisin B1, Sphingolipids, Bile acid, Chemistry, Hepatotoxicity, Fumonisin, food and beverages, Alanine Transaminase, General Medicine, 3. Good health, Mice, Inbred C57BL, 030104 developmental biology, Nuclear receptor, Gene Expression Regulation, Liver, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Toxicity, lipids (amino acids, peptides, and proteins), LXR, Female, Chemical and Drug Induced Liver Injury, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition
Abstract: International audience; Fumonisin B1 (FB1), a congener of fumonisins produced by Fusarium species, is the most abundant and most toxicologically active fumonisin. FB1 causes severe mycotoxicosis in animals, including nephrotoxicity, hepatotoxicity, and disruption of the intestinal barrier. However, mechanisms associated with FB1 toxicity are still unclear. Preliminary studies have highlighted the role of liver X receptors (LXRs) during FB1 exposure. LXRs belong to the nuclear receptor family and control the expression of genes involved in cholesterol and lipid homeostasis. In this context, the toxicity of FB1 was compared in female wild-type (LXR+/+) and LXR, double knockout (LXR-/-) mice in the absence or presence of FB1 (10mg/kg body weight/day) for 28days. Exposure to FB1 supplemented in the mice's drinking water resulted in more pronounced hepatotoxicity in LXR-/- mice compared to LXR+/+ mice, as indicated by hepatic transaminase levels (ALT, AST) and hepatic inflammatory and fibrotic lesions. Next, the effect of FB1 exposure on the liver transcriptome was investigated. FB1 exposure led to a specific transcriptional response in LXR-/- mice that included altered cholesterol and bile acid homeostasis. ELISA showed that these effects were associated with an elevated FB1 concentration in the plasma of LXR-/- mice, suggesting that LXRs participate in intestinal absorption and/or clearance of the toxin. In summary, this study demonstrates an important role of LXRs in protecting the liver against FB1-induced toxicity, suggesting an alternative mechanism not related to the inhibition of sphingolipid synthesis for mycotoxin toxicity.
Published: 2018
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38. Fumonisin-Exposure Impairs Age-Related Ecological Succession of Bacterial Species in Weaned Pig Gut Microbiota

Author: Sylvie Combes, Isabelle P. Oswald, Laurent Cauquil, Joëlle Laffitte, Sara Botti, Céline Barilly, Philippe Pinton, Géraldine Pascal, Anne Marie Cossalter, Iván Mateos, Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Plateforme Ezop (Ezop), ToxAlim (ToxAlim), Université Toulouse III - Paul Sabatier (UT3), 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)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), PTP Science Park, Région Occitanie CLE 2014, ANR Fumolip (ANR-16-CE21-0003), ANR LipoReg (ANR-15-Carn0016), ANR ExpoMycoPig (ANR-17-Carn012), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-École nationale supérieure agronomique de Toulouse [ENSAT]
Subjects: Male, 0301 basic medicine, Aging, MiSeq 16S rDNA sequencing, Swine, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], 030106 microbiology, lcsh:Medicine, Veillonellaceae, Zoology, Weaning, Biology, Gut flora, Toxicology, Fumonisins, Article, Feces, 03 medical and health sciences, chemistry.chemical_compound, Diversity index, fumonisin, fluids and secretions, Lactobacillus, Fumonisin, microbiota, Animals, 2. Zero hunger, lcsh:R, Lachnospiraceae, food and beverages, pigs, biology.organism_classification, Animal Feed, Diet, Gastrointestinal Microbiome, 3. Good health, 030104 developmental biology, chemistry, Toxicity, Roseburia
Abstract: Pigs are highly affected by dietary mycotoxin contamination and particularly by fumonisin. The effects of fumonisin on pig intestinal health are well documented, but little is known regarding its impact on gut microbiota. We investigate the effects of the fumonisin (FB1, 12 mg/kg feed) on the fecal microbiota of piglets (n = 6) after 0, 8, 15, 22, and 29 days of exposure. A control group of six piglets received a diet free of FB1. Bacterial community diversity, structure and taxonomic composition were carried out by V3&ndash, V4 16S rRNA gene sequencing. Exposure to FB1 decreases the diversity index, and shifts and constrains the structure and the composition of the bacterial community. This takes place as early as after 15 days of exposure and is at a maximum after 22 days of exposure. Compared to control, FB1 alters the ecological succession of fecal microbiota species toward higher levels of Lactobacillus and lower levels of the Lachnospiraceae and Veillonellaceae families, and particularly OTUs (Operational Taxonomic Units) of the genera Mitsuokella, Faecalibacterium and Roseburia. In conclusion, FB1 shifts and constrains age-related evolution of microbiota. The direct or indirect contribution of FB1 microbiota alteration in the global host response to FB1 toxicity remains to be investigated.
Published: 2018
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39. Mycotoxins and oxidative stress: where are we?

Author: E.O. da Silva, Ana Paula Frederico Rodrigues Loureiro Bracarense, Isabelle P. Oswald, Laboratory of Animal Pathology, State University of Londrina = Universidade Estadual de Londrina, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), ToxAlim (ToxAlim), 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), Institut National Polytechnique (Toulouse) (Toulouse INP), 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)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), Bracarense, Ana P.F.L., and Oswald, Isabelle P.
Subjects: 0301 basic medicine, Aflatoxin, Antioxidant, DNA damage, medicine.medical_treatment, [SDV]Life Sciences [q-bio], antioxydants, mycotoxins, oxidative stress, Toxicology, medicine.disease_cause, Patulin, Lipid peroxidation, 03 medical and health sciences, chemistry.chemical_compound, 0404 agricultural biotechnology, medicine, Food science, Ochratoxin, Fumonisin B1, Public Health, Environmental and Occupational Health, food and beverages, 04 agricultural and veterinary sciences, 040401 food science, 3. Good health, 030104 developmental biology, chemistry, Oxidative stress, Food Science
Abstract: Mycotoxins are the most common contaminants of food and feed worldwide and are considered an important risk factor for human and animal health. Oxidative stress occurs in cells when the concentration of reactive oxygen species exceeds the cell’s antioxidant capacity. Oxidative stress causes DNA damage, enhances lipid peroxidation, protein damage and cell death. This review addresses the toxicity of the major mycotoxins, especially aflatoxin B1, deoxynivalenol, nivalenol, T-2 toxin, fumonisin B1, ochratoxin, patulin and zearalenone, in relation to oxidative stress. It summarises the data associated with oxidative stress as a plausible mechanism for mycotoxin-induced toxicity. Given the contamination caused by mycotoxins worldwide, the protective effects of a variety of natural compounds due to their antioxidant capacities have been evaluated. We review data on the ability of vitamins, flavonoids, crocin, curcumin, green tea, lycopene, phytic acid, L-carnitine, melatonin, minerals and mixtures of anti-oxidants to mitigate the toxic effect of mycotoxins associated with oxidative stress.
Published: 2018
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40. Analysis of the interactions between environmental and food contaminants, cadmium and deoxynivalenol, in different target organs

Author: Thanh-Huong Le, Isabelle P. Oswald, Philippe Pinton, Imourana Alassane-Kpembi, ToxAlim (ToxAlim), 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), Institut National Polytechnique (Toulouse) (Toulouse INP), 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), Hôpital d’Instruction des Armées (HIA), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), This work was supported, in part, by the French National Research Agency (project CaDON 15-CE21-0001-02) and Partenariat Hubert Curien project (PHC 35813XM). THL was supported by the Ministry of Education and Training of Vietnam and University of Science and Technology of Hanoi (decision 1343/QD-BGDDT), Hôpital d'Instruction des Armées Camp Guézo, Service de Santé des Armées, Partenariat Hubert Curien project (PHC 35813XM), Ministry of Education and Training of Vietnam, University of Science and Technology of Hanoi (decision 1343/QD-BGDDT), and ANR-15-CE21-0001,CaDON,Cadmium et Deoxynivalenol dans les récoltes de blé dur: comprendre les évènements de contamination croisée et évaluer la toxicité du mélange.(2015)
Subjects: 0301 basic medicine, kidney, Environmental Engineering, Cell Survival, cadmium, [SDV.TOX.TVM]Life Sciences [q-bio]/Toxicology/Vegetal toxicology and mycotoxicology, chemistry.chemical_element, interaction, Food Contamination, HL-60 Cells, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, liver, mycotoxin, 03 medical and health sciences, chemistry.chemical_compound, In vivo, blood, Toxicity Tests, medicine, Humans, Environmental Chemistry, Food science, Cytotoxicity, Mycotoxin, Waste Management and Disposal, intestine, Kidney, Cadmium, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Chemistry, toxicity, Hep G2 Cells, Mycotoxins, Pollution, 3. Good health, HEK293 Cells, 030104 developmental biology, medicine.anatomical_structure, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Toxicity, Caco-2 Cells, Trichothecenes, Antagonism, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Food contaminant
Abstract: International audience; Cadmium (Cd), a common and widespread toxic heavy metal, and mycotoxins such as deoxynivalenol (DON) are frequent contaminants of the food supply. Most of the data on their toxicity concern their effects when present alone. However, consumers can be exposed to a cocktail of DON and Cd. To improve the understanding of their combined toxicity, the effects of DON and Cd alone or in combination were investigated in different human cell lines from the kidney (HEK-293), intestine (Caco-2), blood (HL-60) and liver (HepG2). Cytotoxicity was assessed through ATP measurement and types of interactions determined by the Isobologram-Combination index method. HEK-293 cells were exposed to increasing doses of DON, Cd and their combination at different ratios (DON/Cd of 2/1; 1/1; 1/2 and 1/8). Regardless of the ratio, the type of interaction observed in HEK-293 cells ranged from moderate antagonism to nearly additive with increasing cytotoxicity. In Caco-2 cells, the interactions ranged from nearly additive to antagonism whatever the ratio. At ratio 1/1, in HL-60 and HepG2 cells, interactions ranged from synergy to antagonism depending on the cytotoxicity level. Using human cells lines, this study indicates that the consequences of combined exposure to environmental and food contaminants are specific to the target organ. Further studies are needed to confirm these data in vivo.
Published: 2018
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41. Porcine small and large intestinal microbiota rapidly hydrolyze the masked mycotoxin deoxynivalenol-3-glucoside and release deoxynivalenol in spiked batch cultures in vitro

Author: Anthony J. Richardson, Isabelle P. Oswald, Valerie Currie, Freda M. Farquharson, Silvia W. Gratz, Grietje Holtrop, Philippe Pinton, Petra Louis, Gary Duncan, University of Aberdeen, Biomathematics and Statistics Scotland, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), 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)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, and This study was supported by the Scottish Government Rural and Environment Science and Analytical Services Division (RESAS) and by the French Agence Nationale de la Recherche (project ANR-13-CESA-0003-03)
Subjects: 0301 basic medicine, pig, Swine, [SDV]Life Sciences [q-bio], 030106 microbiology, Trichothecene, trichothecene, Food Contamination, Ileum, Biology, Polymerase Chain Reaction, Applied Microbiology and Biotechnology, digestive system, release, Microbiology, Jejunum, Feces, 03 medical and health sciences, chemistry.chemical_compound, Cecum, Glucosides, deoxynivalenol-3-glucoside, medicine, microbiota, Animals, Humans, Large intestine, Anaerobiosis, Mycotoxin, Ecology, Hydrolysis, food and beverages, toxicity, Mycotoxins, Small intestine, Gastrointestinal Microbiome, Intestines, masked mycotoxin, 030104 developmental biology, medicine.anatomical_structure, chemistry, Batch Cell Culture Techniques, Food Microbiology, Edible Grain, Trichothecenes, Food Science, Biotechnology
Abstract: Mycotoxin contamination of cereal grains causes well-recognized toxicities in animals and humans, but the fate of plant-bound masked mycotoxins in the gut is less well understood. Masked mycotoxins have been found to be stable under conditions prevailing in the small intestine but are rapidly hydrolyzed by fecal microbiota. This study aims to assess the hydrolysis of the masked mycotoxin deoxynivalenol-3-glucoside (DON3Glc) by the microbiota of different regions of the porcine intestinal tract. Intestinal digesta samples were collected from the jejunum, ileum, cecum, colon, and feces of 5 pigs and immediately frozen under anaerobic conditions. Sample slurries were prepared in M2 culture medium, spiked with DON3Glc or free deoxynivalenol (DON; 2 nmol/ml), and incubated anaerobically for up to 72 h. Mycotoxin concentrations were determined using liquid chromatography-tandem mass spectrometry, and the microbiota composition was determined using a quantitative PCR methodology. The jejunal microbiota hydrolyzed DON3Glc very slowly, while samples from the ileum, cecum, colon, and feces rapidly and efficiently hydrolyzed DON3Glc. No further metabolism of DON was observed in any sample. The microbial load and microbiota composition in the ileum were significantly different from those in the distal intestinal regions, whereas those in the cecum, colon and feces did not differ. IMPORTANCE Results from this study clearly demonstrate that the masked mycotoxin DON3Glc is hydrolyzed efficiently in the distal small intestine and large intestine of pigs. Once DON is released, toxicity and absorption in the distal intestinal tract likely occur in vivo . This study further supports the need to include masked metabolites in mycotoxin risk assessments and regulatory actions for feed and food.
Published: 2018
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42. Risks for animal health related to the presence of fumonisins, their modified forms and hidden forms in feed

Author: EFSA Panel on Contaminants in the Food Chain (CONTAM), Helle‐Katrine Knutsen, Jan Alexander, Lars Barregård, Margherita Bignami, Beat Brüschweiler, Sandra Ceccatelli, Bruce Cottrill, Michael Dinovi, Lutz Edler, Bettina Grasl‐Kraupp, Christer Hogstrand, Laurentius (Ron) Hoogenboom, Carlo Stefano Nebbia, Annette Petersen, Martin Rose, Alain‐Claude Roudot, Tanja Schwerdtle, Christiane Vleminckx, Günter Vollmer, Heather Wallace, Chiara Dall'Asta, Gunnar‐Sundstøl Eriksen, Ionelia Taranu, Andrea Altieri, Ruth Roldán‐Torres, Isabelle P Oswald, Norwegian Institute of Public Health [Oslo] (NIPH), German Cancer Research Center, Division of Biostatistics, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), ToxAlim (ToxAlim), 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), Institut National Polytechnique (Toulouse) (Toulouse INP), 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)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)
Subjects: Veterinary medicine, Novel Foods & Agrochains, Plant Science, Novel Foods & Agroketens, 01 natural sciences, Food chain, chemistry.chemical_compound, TX341-641, BU Toxicology, Novel Foods & Agrochains, Mink, 2. Zero hunger, biology, Animal health, Dietary exposure, hidden forms, BU Toxicology, feed, food and beverages, modified forms, 04 agricultural and veterinary sciences, 040401 food science, Chemical Contaminants, BU Toxicologie, Novel Foods & Agroketens, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Fusarium, BU Toxicologie, Veterinary (miscellaneous), Fusarium proliferatum, [SDV.TOX.TVM]Life Sciences [q-bio]/Toxicology/Vegetal toxicology and mycotoxicology, TP1-1185, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, Microbiology, 0404 agricultural biotechnology, SDG 3 - Good Health and Well-being, biology.animal, Mycotoxin, VLAG, Fumonisin B1, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, Nutrition. Foods and food supply, Chemical technology, 010401 analytical chemistry, toxicity, biology.organism_classification, 0104 chemical sciences, Scientific Opinion, chemistry, exposure, Animal Science and Zoology, Parasitology, fumonisins, animal health risk assessment, Food Science
Abstract: International audience; Fumonisins, mycotoxins primarily produced by Fusarium verticillioides and Fusarium proliferatum, occur predominantly in cereal grains, especially in maize. The European Commission asked EFSA for a scientific opinion on the risk to animal health related to fumonisins and their modified and hidden forms in feed. Fumonisin B 1 (FB 1), FB 2 and FB 3 are the most common forms of fumonisins in feedstuffs and thus were included in the assessment. FB 1 , FB 2 and FB 3 have the same mode of action and were considered as having similar toxicological profile and potencies. For fumonisins, the EFSA Panel on Contaminants in the Food Chain (CONTAM) identified no-observed-adverse-effect levels (NOAELs) for cattle, pig, poultry (chicken, ducks and turkeys), horse, and lowest-observed-adverseeffect levels (LOAELs) for fish (extrapolated from carp) and rabbits. No reference points could be identified for sheep, goats, dogs, cats and mink. The dietary exposure was estimated on 18,140 feed samples on FB 1-3 representing most of the feed commodities with potential presence of fumonisins. Samples were collected between 2003 and 2016 from 19 different European countries, but most of them from four Member States. To take into account the possible occurrence of hidden forms, an additional factor of 1.6, derived from the literature, was applied to the occurrence data. Modified forms of fumonisins, for which no data were identified concerning both the occurrence and the toxicity, were not included in the assessment. Based on mean exposure estimates, the risk of adverse health effects of feeds containing FB 1-3 was considered very low for ruminants, low for poultry, horse, rabbits, fish and of potential concern for pigs. The same conclusions apply to the sum of FB 1-3 and their hidden forms, except for pigs for which the risk of adverse health effect was considered of concern.
Published: 2018
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43. The importance of accounting for sex in the search of proteomic signatures of mycotoxin exposure

Author: Isabelle P. Oswald, Laura Soler, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), ToxAlim (ToxAlim), 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), Institut National Polytechnique (Toulouse) (Toulouse INP), 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)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA), and Oswald, Isabelle P.
Subjects: 0301 basic medicine, Male, [SDV]Life Sciences [q-bio], Biophysics, Accounting, Food Contamination, medicine.disease_cause, Proteomics, Biochemistry, endocrine disruptor, genotoxicity, immunotoxicity, mycotoxins, proteomics, sexual-dimorphism, Patulin, 03 medical and health sciences, Mycotoxicology, chemistry.chemical_compound, Sex Factors, medicine, Animals, Humans, Mycotoxin, Fumonisin B1, 030102 biochemistry & molecular biology, biology, business.industry, Toxin, food and beverages, Environmental Exposure, biology.organism_classification, 030104 developmental biology, Endocrine disruptor, chemistry, Proteome, Female, business, Biomarkers
Abstract: Mycotoxins are natural food and feed contaminants that are toxic to human and animals. Proteomics is an adequate toolbox to investigate the mode of action and the effects of mycotoxins, as these toxicants often alter protein synthesis and degradation, as well as induce changes of important post-translational modifications. For instance, the contaminant deoxynivalenol induces a severe ribosomal stress that affects protein production, whereas the toxin Fumonisin B1 can alter the phosphorylation of a large number of proteins, and patulin is a potent proteotoxic molecule. The response to most mycotoxins is sex-dependent, males being generally more sensitive than females. In addition, for some toxins, the toxic effects observed were different for each sex. Nevertheless, the importance of accounting for a sex-dependent response is often overlooked in toxicology studies involving mycotoxins. Here we review the information that proteomics has provided in pre-clinical studies of mycotoxin exposure as well as the differential response of males and females to these molecules to highlight the need of including male and female individuals when evaluating the impact of mycotoxins in the cell proteome. Significance The current trend in mycotoxicology is the combination of several -omics techniques in order to understand the mechanism of action and effects of these toxic natural food contaminants. One of the goals of these experiments is to determine “potential biomarkers” of mycotoxicoses. Nevertheless, the strategy followed in biomarker research must take into account as many possible factors as possible in order to find robust biomarkers for differential diagnosis. Among the factors that can have an influence in the response to mycotoxins, one of the most important is sex. Traditionally, males are preferentially used in research, as they are more sensitive to mycotoxins and their response is not dependent on hormonal levels, thus less variable. However the intrinsic and hormonal differences between sexes makes that results obtained in males are often not directly transferrable to females. In this review, we want to highlight (1) that proteomics has a great potential on mycotoxin research, and (2) the need in taking into account sex differences in proteomic studies, mostly when the discovery of robust biomarkers of mycotoxins response is desired.
Published: 2018
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44. Genotoxicity of aflatoxins and their precursors in human cells

Author: Cécile Canlet, Marc Audebert, Olivier Puel, Isabelle P. Oswald, Selma P. Snini, Souria Tadrist, Martin G. Theumer, Laure Khoury, Yasmine Henneb, ToxAlim (ToxAlim), Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Ecole d'Ingénieurs de Purpan (INPT - EI Purpan), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Analyse de Xénobiotiques, Identification, Métabolisme (E20 Metatoul-AXIOM), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaToul-MetaboHUB, Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Métabolisme et Xénobiotiques (ToxAlim-MeX), ProdInra, Migration, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-MetaboHUB-MetaToul, Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Génopole Toulouse Midi-Pyrénées [Auzeville] (GENOTOUL), and Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: 0301 basic medicine, Aflatoxin, Aflatoxin B1, Sterigmatocystin, [SDV]Life Sciences [q-bio], GENOTOXICITY, Anthraquinones, Toxicology, medicine.disease_cause, Activation, Metabolic, Histones, chemistry.chemical_compound, Aflatoxins, heterocyclic compounds, H2AX, Cytotoxicity, Chemistry, food and beverages, Hep G2 Cells, 04 agricultural and veterinary sciences, General Medicine, Bioquímica y Biología Molecular, 040401 food science, 3. Good health, [SDV] Life Sciences [q-bio], Biochemistry, Biological Assay, Micología, CIENCIAS NATURALES Y EXACTAS, Cell Survival, DNA damage, METABOLISM, Risk Assessment, DNA DAMAGE, Ciencias Biológicas, 03 medical and health sciences, 0404 agricultural biotechnology, medicine, Humans, Carcinogen, Dose-Response Relationship, Drug, Mutagenicity Tests, genotoxicity, technology, industry, and agriculture, aflatoxin, Metabolism, biological factors, AFLATOXIN, 030104 developmental biology, Cell culture, metabolism, Biomarkers, Genotoxicity
Abstract: Aflatoxins are found as food contaminant and some of them demonstrate a carcinogenic effect. The aflatoxins biosynthetic pathway involves 15 successive steps. The aim of this study was to compare the toxicity of aflatoxins and their precursors in three human cell lines. We tested the four aflatoxins and two of their metabolites; three early metabolic precursors and two late biosynthetic precursors. Cyclopiazonic acid, synthesized in parallel with aflatoxins, was also tested. The cytotoxicity and the genotoxicity was evaluated with the γH2AX assay in three human cell lines with different bioactivation capacities. Our results indicated that the most genotoxic chemicals in the three cell lines were in decreasing order sterigmatocystin (ST), aflatoxin B1 (AFB1), aflatoxicol (AFL), aflatoxin G1 (AFG1) and versicolorin A (VERA). Aflatoxin M1 (AFM1) demonstrated genotoxic property in only one cell line. The other tested compounds did not demonstrate any genotoxic activity. Overall, our results suggested different genotoxic mechanisms of action for the tested compounds, involving specific bioactivation pathways. Moreover, some metabolic precursors of aflatoxins demonstrated genotoxic potential equivalent or greater to AFB1. This should be taking into account for the development of new strategies intended to reduce the aflatoxins exposure and for human risk assessment. Fil: Theumer, Martín Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Córdoba. Centro de Investigaciones en Bioquímica Clínica e Inmunología; Argentina. Université de Toulouse; Francia. Institut National de la Recherche Agronomique; Francia Fil: Henneb, Y.. Institut National de la Recherche Agronomique; Francia. Université de Toulouse; Francia Fil: Khoury, L.. Institut National de la Recherche Agronomique; Francia. Université de Toulouse; Francia Fil: Snini, S.P.. Université de Toulouse; Francia. Institut National de la Recherche Agronomique; Francia Fil: Tadrist, S.. Institut National de la Recherche Agronomique; Francia. Université de Toulouse; Francia Fil: Canlet, C.. Institut National de la Recherche Agronomique; Francia. Université de Toulouse; Francia Fil: Puel, O.. Université de Toulouse; Francia. Institut National de la Recherche Agronomique; Francia Fil: Oswald, I.P.. Institut National de la Recherche Agronomique; Francia. Université de Toulouse; Francia Fil: Audebert, M.. Institut National de la Recherche Agronomique; Francia. Université de Toulouse; Francia
Published: 2018
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45. Update of the risk assessment on 3‐monochloropropane diol and its fatty acid esters

Author: EFSA Panel on Contaminants in the Food Chain (CONTAM), Helle Katrine Knutsen, Jan Alexander, Lars Barregård, Margherita Bignami, Beat Brüschweiler, Sandra Ceccatelli, Bruce Cottrill, Michael Dinovi, Lutz Edler, Bettina Grasl‐Kraupp, Laurentius (Ron) Hoogenboom, Carlo Stefano Nebbia, Isabelle P Oswald, Annette Petersen, Martin Rose, Alain‐Claude Roudot, Tanja Schwerdtle, Christiane Vleminckx, Günter Vollmer, Heather Wallace, Alfonso Lampen, Ian Morris, Aldert Piersma, Dieter Schrenk, Marco Binaglia, Sara Levorato, and Christer Hogstrand
Subjects: Novel Foods & Agrochains, BU Toxicologie, 3‐MCPD, Veterinary (miscellaneous), Diol, TP1-1185, Plant Science, fatty acid esters, Novel Foods & Agroketens, Microbiology, process contaminant, Benford's law, 03 medical and health sciences, chemistry.chemical_compound, 3-MCPD, 0404 agricultural biotechnology, 0302 clinical medicine, TX341-641, BU Toxicology, Novel Foods & Agrochains, refined vegetable oils, VLAG, chemistry.chemical_classification, 030219 obstetrics & reproductive medicine, Actuarial science, benchmark dose, Nutrition. Foods and food supply, Chemical technology, BU Toxicology, Fatty acid, risk assessment, 04 agricultural and veterinary sciences, 040401 food science, Scientific Opinion, BU Toxicologie, Novel Foods & Agroketens, chemistry, Animal Science and Zoology, Parasitology, Psychology, Risk assessment, Food Science
Abstract: The CONTAM Panel updated the assessment of the risks for human health related to the presence of 3‐monochloropropane diol (3‐MCPD) and its fatty acid esters in food published in 2016 in view of the scientific divergence identified in the establishment of the tolerable daily intake (TDI) in the Joint FAO/WHO Expert Committee on Food Additives and Contaminants (FAO/WHO) report published in 2017. In this update, dose–response analysis was performed following the recent EFSA Scientific Committee guidance on the use of benchmark dose (BMD) approach in risk assessment, and a review of available data on developmental and reproduction toxicity was included. The outcome of this review indicates that in rats short‐term exposure to 3‐MCPD above 1 mg/kg body weight (bw) per day can induce reduced sperm motility associated with reduced male fecundity. Decreased sperm count and histopathological changes in the testis and epididymis were observed following longer treatment periods at higher doses. Regarding increased incidence kidney tubular hyperplasia, BMD analysis using model averaging resulted in a BMDL 10 of 0.20 mg/kg bw per day in male rats, which was selected as the new Reference Point (RP) for renal effects. For the effects on male fertility, decreased sperm motility was selected as the most sensitive relevant endpoint and a BMDL 05 of 0.44 mg/kg bw per day was calculated. The RP for renal effects was considered to derive an updated group TDI of 2 μg/kg bw per day for 3‐MCPD and its fatty acid esters and was considered protective also for effects on male fertility. The established TDI of 2 μg/kg bw per day is not exceeded in the adult population. A slight exceedance of the TDI was observed in the high consumers of the younger age groups and in particular for the scenarios on infants receiving formula only., This publication is linked to the following EFSA Journal article: http://onlinelibrary.wiley.com/doi/10.2903/j.efsa.2016.4426/full
Published: 2018

46. Patulin is a cultivar-dependent aggressiveness factor favouring the colonization of apples byPenicillium expansum

Author: Joanna Tannous, Sylviane Bailly, Pauline Heuillard, Olivier Puel, Christian Barreau, Enric Zehraoui, Selma P. Snini, Yannick Lippi, and Isabelle P. Oswald
Subjects: 0301 basic medicine, Malus, Strain (chemistry), fungi, 030106 microbiology, Mutant, food and beverages, Soil Science, Virulence, Plant Science, Biology, biology.organism_classification, Microbiology, Patulin, 03 medical and health sciences, chemistry.chemical_compound, chemistry, Penicillium, bacteria, Penicillium expansum, Mycotoxin, Agronomy and Crop Science, Molecular Biology
Abstract: The blue mould decay of apples is caused by Penicillium expansum and is associated with contamination by patulin, a worldwide regulated mycotoxin. Recently, a cluster of 15 genes (patA-patO) involved in patulin biosynthesis was identified in P. expansum. blast analysis revealed that patL encodes a Cys6 zinc finger regulatory factor. The deletion of patL caused a drastic decrease in the expression of all pat genes, leading to an absence of patulin production. Pathogenicity studies performed on 13 apple varieties indicated that the PeΔpatL strain could still infect apples, but the intensity of symptoms was weaker compared with the wild-type strain. A lower growth rate was observed in the PeΔpatL strain when this strain was grown on nine of the 13 apple varieties tested. In the complemented PeΔpatL:patL strain, the ability to grow normally in apple and the production of patulin were restored. Our results clearly demonstrate that patulin is not indispensable in the initiation of the disease, but acts as a cultivar-dependent aggressiveness factor for P. expansum. This conclusion was strengthened by the fact that the addition of patulin to apple infected by the PeΔpatL mutant restored the normal fungal colonization in apple.
Published: 2015
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47. Response of Deeproot Sedge (Cyperus entrerianus) to Herbicide and Prescribed Fire in Texas Coastal Prairie

Author: Andrew J. Bennett, Warren C. Conway, David J. Rosen, Jonathan R. King, and Brian P. Oswald
Subjects: 0106 biological sciences, Dormant season, 04 agricultural and veterinary sciences, Plant Science, Imazapic, 010603 evolutionary biology, 01 natural sciences, Invasive species, Cyperus entrerianus, chemistry.chemical_compound, chemistry, Habitat, Agronomy, 040103 agronomy & agriculture, Temperate climate, 0401 agriculture, forestry, and fisheries, Environmental science, Monoculture, Woody plant
Abstract: Introduced accidentally from South America, deeproot sedge is rapidly expanding in a variety of habitats throughout the southeastern United States. Of particular concern is its rapid expansion, naturalization, and formation of monocultures in Texas coastal prairie, one of the most imperiled temperate ecoregions in North America. The objective of this research was to examine how deeproot sedge responds to prescribed fire, to the herbicide imazapic, and to treatment combinations of both. Combinations of prescribed fire and imazapic treatments and imazapic-only treatments effectively reduced deeproot sedge cover and frequency. However, plots exposed to dormant season fires (with no imazapic) had greater deeproot sedge cover after burn treatments were applied, indicating that coastal prairie management using only dormant season prescribed fire will not work toward reduction or management of this exotic invasive species. Although deeproot sedge cover was often reduced in fire–imazapic treatment combinations, it was still present in treatment plots. Moreover, desirable functional plant groups (i.e., native bunchgrasses) did not respond positively to the fire–imazapic treatments, but in some instances, woody plant coverage increased. Repeated, long-term approaches using integrated and coordinated efforts with multiple treatment options will be necessary to restore community structure to desired compositional levels. Such integrated approaches should be effective in reducing deeproot sedge frequency, cover, and extent to more manageable levels throughout its introduced geographic range.
Published: 2015
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48. Aspergillus korhogoensis, a Novel Aflatoxin Producing Species from the Côte d’Ivoire

Author: David Akaki, Rose Koffi-Nevry, S. O. Fapohunda, Isabelle P. Oswald, Didier Montet, Amaranta Carvajal-Campos, Sophie Lorber, Sylviane Bailly, Ama Lethicia Manizan, Catherine Brabet, Olivier Puel, Souria Tadrist, Geromy G. Moore, ToxAlim (ToxAlim), 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), Institut National Polytechnique (Toulouse) (Toulouse INP), 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), Université Nangui Abrogoua, Institut National Polytechnique Félix Houphouët-Boigny, United States Department of Agriculture (USDA), Babcock University, Qualisud - Pôle de La Réunion (Qualisud Réunion), Démarche intégrée pour l'obtention d'aliments de qualité (UMR Qualisud), Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de La Réunion (UR)-Université de Montpellier (UM)-Avignon Université (AU)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1)-Centre de Coopération Internationale en Recherche Agronomique pour le Développement (Cirad)-Institut national d’études supérieures agronomiques de Montpellier (Montpellier SupAgro), Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Université de La Réunion (UR)-Université de Montpellier (UM)-Avignon Université (AU)-Centre international d'études supérieures en sciences agronomiques (Montpellier SupAgro)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3), and Puel, Olivier
Subjects: 0301 basic medicine, aflatoxins, Arachis, Health, Toxicology and Mutagenesis, [SDV]Life Sciences [q-bio], Genes, Fungal, Secondary Metabolism, lcsh:Medicine, Locus (genetics), Food Contamination, Toxicology, Aspergillic acid, cyclopiazonic acid, Article, 03 medical and health sciences, Monophyly, chemistry.chemical_compound, Botany, Heterothallic, Amino Acid Sequence, aspergillus section Flavi, polyphasic approach, versicolorins, Aspergillus section Flavi, côte d'ivoire, Phylogeny, Aspergillus, Phylogenetic tree, biology, lcsh:R, biology.organism_classification, Arachis hypogaea, 030104 developmental biology, Cote d'Ivoire, Sister group, chemistry, Q53 - Contamination et toxicologie des aliments pour animaux
Abstract: International audience; Several strains of a new aflatoxigenic species of Aspergillus, A. korhogoensis, were isolated in the course of a screening study involving species from section Flavi found contaminating peanuts (Arachis hypogaea) and peanut paste in the Côte d'Ivoire. Based on examination of four isolates, this new species is described using a polyphasic approach. A concatenated alignment comprised of nine genes (ITS, benA, cmdA, mcm7, amdS, rpb1, preB, ppgA, and preA) was subjected to phylogenetic analysis, and resulted in all four strains being inferred as a distinct clade. Characterization of mating type for each strain revealed A. korhogoensis as a heterothallic species, since three isolates exhibited a singular MAT1-1 locus and one isolate exhibited a singular MAT1-2 locus. Morphological and physiological characterizations were also performed based on their growth on various types of media. Their respective extrolite profiles were characterized using LC/HRMS, and showed that this new species is capable of producing B- and G-aflatoxins, aspergillic acid, cyclopiazonic acid, aflavarins, and asparasones, as well as other metabolites. Altogether, our results confirm the monophyly of A. korhogoensis, and strengthen its position in the A. flavus clade, as the sister taxon of A. parvisclerotigenus.
Published: 2017
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49. Risks to human and animal health related to the presence of deoxynivalenol and its acetylated and modified forms in food and feed

Author: Bistra Benkova, Annette Petersen, Luisa Ramos Bordajandi, Margherita Bignami, Karsten Meyer, Jan Alexander, Hanspeter Naegeli, Bruce Cottrill, Sandra Ceccatelli, Beat Johannes Brüschweiler, Yun Yun Gong, Andrea Altieri, Petra Gergelova, Michael Dinovi, Alain-Claude Roudot, Sarah De Saeger, Mathijs van Manen, Martin Rose, Dominique Parent-Massin, Hans P. van Egmond, Lars Barregård, Günter Vollmer, Athanasios Gkrillas, Christer Hogstrand, Christiane Vleminckx, Isabelle P Oswald, Heather M. Wallace, Jean-Marc Fremy, Ivonne M.C.M. Rietjens, Nicklas Gustavsson, Barbara Dörr, Laurentius Hoogenboom, Carlo Nebbia, Tanja Schwerdtle, Peter B. Farmer, Mari Eskola, Gunnar Sundstøl Eriksen, Bettina Grasl-Kraupp, Helle Katrine Knutsen, Lutz Edler, King‘s College London, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), ToxAlim (ToxAlim), 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), Institut National Polytechnique (Toulouse) (Toulouse INP), 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)-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)
Subjects: Fusarium, medicine.medical_specialty, Veterinary (miscellaneous), Fish farming, [SDV.TOX.TVM]Life Sciences [q-bio]/Toxicology/Vegetal toxicology and mycotoxicology, Forage, Plant Science, [SDV.TOX.TCA]Life Sciences [q-bio]/Toxicology/Toxicology and food chain, Microbiology, Toxicology, chemistry.chemical_compound, 0404 agricultural biotechnology, biology.animal, Epidemiology, medicine, Mink, human and animal risk assessment, Mycotoxin, Adverse effect, 2. Zero hunger, 15‐acetyl‐deoxynivalenol, [SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health, biology, deoxynivalenol-3glucoside, deoxynivalenol‐3‐glucoside, food and beverages, toxicity, 04 agricultural and veterinary sciences, biology.organism_classification, 040401 food science, Deoxynivalenol, 3. Good health, 15-acetyl-deoxynivalenol, Scientific Opinion, chemistry, exposure, [SDV.TOX]Life Sciences [q-bio]/Toxicology, Toxicity, 3‐acetyl‐deoxynivalenol, 3-acetyl-deoxynivalenol, Animal Science and Zoology, Parasitology, Food Science
Abstract: International audience; Deoxynivalenol (DON) is a mycotoxin primarily produced by Fusarium fungi, occurring predominantly in cereal grains. Following the request of the European Commission, the CONTAM Panel assessed the risk to animal and human health related to DON, 3-acetyl-DON (3-Ac-DON), 15-acetyl-DON (15-Ac-DON) and DON-3-glucoside in food and feed. A total of 27,537, 13,892, 7,270 and 2,266 analytical data for DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside, respectively, in food, feed and unprocessed grains collected from 2007 to 2014 were used. For human exposure, grains and grain-based products were main sources, whereas in farm and companion animals, cereal grains, cereal by-products and forage maize contributed most. DON is rapidly absorbed, distributed, and excreted. Since 3-Ac-DON and 15-Ac-DON are largely deacetylated and DON-3-glucoside cleaved in the intestines the same toxic effects as DON can be expected. The TDI of 1 lg/kg bw per day, that was established for DON based on reduced body weight gain in mice, was therefore used as a group-TDI for the sum of DON, 3-Ac-DON, 15-Ac-DON and DON-3-glucoside. In order to assess acute human health risk, epidemiological data from mycotoxicoses were assessed and a group-ARfD of 8 lg/kg bw per eating occasion was calculated. Estimates of acute dietary exposures were below this dose and did not raise a health concern in humans. The estimated mean chronic dietary exposure was above the group-TDI in infants, toddlers and other children, and at high exposure also in adolescents and adults, indicating a potential health concern. Based on estimated mean dietary concentrations in ruminants, poultry, rabbits, dogs and cats, most farmed fish species and horses, adverse effects are not expected. At the high dietary concentrations, there is a potential risk for chronic adverse effects in pigs and fish and for acute adverse effects in cats and farmed mink.
Published: 2017
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50. Aerosolization of Mycotoxins after Growth of Toxinogenic Fungi on Wallpaper

Author: Jean-Denis Bailly, Sebastien Ritoux, Marjorie Draghi, Sylviane Bailly, Isabelle P. Oswald, Marlène Z. Lacroix, Brankica Aleksic, Enric Robine, ToxAlim (ToxAlim), 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), Institut National Polytechnique (Toulouse) (Toulouse INP), 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), Agence de l'Environnement et de la Maîtrise de l'Energie (ADEME), Airborne Pollutants and Bioaerosol Division, Scientific and Technical Centre for Building, This work was financed by the French Ministry of Ecology, Sustainable Development and Energy (PRIMEQUAL project DSC-BIO/2013-121), the French Environment and Energy Management agency (ADEME), and the Scientific and Technical Centre for Building (CSTB) (Ph.D. grant for B. Aleksic), Bailly, Jean-Denis, Biosynthèse & Toxicité des Mycotoxines (ToxAlim-BioToMyc), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Université Toulouse III - Paul Sabatier (UT3)
Subjects: wallpaper, 0301 basic medicine, [SDV]Life Sciences [q-bio], Stachybotrys chartarum, 030106 microbiology, Penicillium brevicompactum, indoor air, 010501 environmental sciences, complex mixtures, 01 natural sciences, Applied Microbiology and Biotechnology, Toxicology, 03 medical and health sciences, chemistry.chemical_compound, mycotoxins, Satratoxin-H, Food science, aerosolization, Mycotoxin, Aerosolization, 0105 earth and related environmental sciences, Ecology, biology, Public and Environmental Health Microbiology, fungi, food and beverages, biology.organism_classification, Spore, chemistry, exposure, 13. Climate action, Aspergillus versicolor, Food Science, Biotechnology, Sterigmatocystin
Abstract: Many fungi can develop on building material in indoor environments if the moisture level is high enough. Among species that are frequently observed, some are known to be potent mycotoxin producers. This presence of toxinogenic fungi in indoor environments raises the question of the possible exposure of occupants to these toxic compounds by inhalation after aerosolization. This study investigated mycotoxin production by Penicillium brevicompactum , Aspergillus versicolor , and Stachybotrys chartarum during their growth on wallpaper and the possible subsequent aerosolization of produced mycotoxins from contaminated substrates. We demonstrated that mycophenolic acid, sterigmatocystin, and macrocyclic trichothecenes (sum of 4 major compounds) could be produced at levels of 1.8, 112.1, and 27.8 mg/m 2 , respectively, on wallpaper. Moreover, part of the produced toxins could be aerosolized from the substrate. The propensity for aerosolization differed according to the fungal species. Thus, particles were aerosolized from wallpaper contaminated with P. brevicompactum when an air velocity of just 0.3 m/s was applied, whereas S. chartarum required an air velocity of 5.9 m/s. A. versicolor was intermediate, since aerosolization occurred under an air velocity of 2 m/s. Quantification of the toxic content revealed that toxic load was mostly associated with particles of size ≥3 μm, which may correspond to spores. However, some macrocyclic trichothecenes (especially satratoxin H and verrucarin J) can also be found on smaller particles that can deeply penetrate the respiratory tract upon inhalation. These elements are important for risk assessment related to moldy environments. IMPORTANCE The possible colonization of building material by toxinogenic fungi in cases of moistening raises the question of the subsequent exposure of occupants to aerosolized mycotoxins. In this study, we demonstrated that three different toxinogenic species produce mycotoxins during their development on wallpaper. These toxins can subsequently be aerosolized, at least partly, from moldy material. This transfer to air requires air velocities that can be encountered under real-life conditions in buildings. Most of the aerosolized toxic load is found in particles whose size corresponds to spores or mycelium fragments. However, some toxins were also found on particles smaller than spores that are easily respirable and can deeply penetrate the human respiratory tract. All of these data are important for risk assessment related to fungal contamination of indoor environments.
Published: 2017
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