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Isabelle Severin

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#### **Domaines d'activités** L'**évaluation du risque** des substances intentionnelles ou non retrouvées dans les aliments est un processus multi-étapes, validé internationalement. Parmi celles-ci, **la caractérisation du danger** se fait à l'aide de **tests toxicologiques**, qui peuvent se réaliser *in vitro* sur des cellules en culture. Le premier effet recherché lors du processus de développement d'un nouveau composé chimique est **la génotoxicité**, c'est à dire la capacité de la molécule à interagir avec le matériel génétique d'une cellule, soit sous sa forme d'ADN double brin, soit condensé en chromosomes. Cette interaction peut amener à une lésion, qui, si elle n'est pas réparée et/ou si la cellule ne meurt pas, peut se transformer en mutation, première étape du développement du processus cancéreux. Parmi les nombreuses sources de contaminants potentiels des aliments, **les emballages** sont souvent incriminés. En effet, des substances chimiques présentes dans les matériaux au contact des denrées alimentaires (MCDA) peuvent migrer vers les aliments. Ces composés, retrouvés en très faibles quantités, peuvent cependant induire des modifications organoleptiques inacceptables, être toxiques par eux-mêmes ou par les produits générés. L’étude du danger que représente l'ensemble des substances capables de migrer de l'emballage vers l'aliment permet une meilleure évaluation de l'emballage fini. Les effets toxiques potentiels des extraits des emballages finis peuvent donc être testés d’un point de vue toxicologique en utilisant des tests de screening *in vitro*, précoces, sensibles et spécifiques, dénommés « **biotests** ». Certains sont déjà utilisés pour les dossiers d’autorisation pour les substances intentionnelles. Les résultats des biotests peuvent être corrélés aux données analytiques afin d’identifier le ou les substances responsables. Si les données analytiques n’expliquent pas l’effet toxique observé, il peut être dû soit à une substance non identifiée dans le mélange, soit à un effet « **cocktail** ». Cette approche s’applique également à d’autres domaines comme les matériaux utilisés en cosmétique ou pour les dispositifs médicaux … . **Recherche** Développement et réalisation de tests de génotoxicité *in vitro, d*epuis la détection de simples cassures de l'ADN jusqu'à la présence de mutations géniques ou chromosomiques/génomiques, voire même l'activation précoce de gènes impliqués dans les processus de réparation de l'ADN. #### **Enseignement** \- Toxicologie alimentaire \- Emballages à contact alimentaire

Publications

Stratégie pour une sécurité chimique intégrée des matériaux d’emballage au contact des denrées alimentaires

Isabelle Séverin , Laurence Dahbi , Sandra Domenek , Phuong-Mai Nguyen , Anne Platel et al.
Cahiers de Nutrition et de Diététique, inPress, ⟨10.1016/j.cnd.2022.12.005⟩
Journal articles hal-03927663v1

In vitro and in silico approach to study the hormonal activities of the alternative plasticizer tri-(2-ethylhexyl) trimellitate TEHTM and its metabolites

Laurence Dahbi , Amaury Farce , Nicolas Kambia , Isabelle Séverin , Thierry Dine et al.
Archives of Toxicology, 2022, 96, pp.899-918. ⟨10.1007/s00204-022-03230-4⟩
Journal articles hal-03546832v1
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Comparative Effects of Di-(2-ethylhexyl)phthalate and Di-(2-ethylhexyl)terephthalate Metabolites on Thyroid Receptors: In Vitro and In Silico Studies

Nicolas Kambia , Isabelle Séverin , Amaury Farce , Laurence Dahbi , Thierry Dine et al.
Metabolites, 2021, 11 (2), pp.94. ⟨10.3390/metabo11020094⟩
Journal articles hal-03141182v1

Development of a new methodology to determine size differences of nanoparticles with nanoparticle tracking analysis

Yann Pellequer , Gilbert Zanetta , Jean-Michel Rebibou , Isabelle Séverin , Marie-Christine Chagnon et al.
Applied Nanoscience, 2021, 11, pp.2129-2141. ⟨10.1007/s13204-021-01932-2⟩
Journal articles hal-03281325v1
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Multigenerational study of the obesogen effects of bisphenol S after a perinatal exposure in C57BL6/J mice fed a high fat diet

Axelle Brulport , Ludovic Le Corre , Guillaume Maquart , Virginie Barbet , Aurélie Dastugue et al.
Environmental Pollution, 2021, 270, pp.116243. ⟨10.1016/j.envpol.2020.116243⟩
Journal articles hal-03148322v1
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Lemon Juice, Sesame Paste, and Autoclaving Influence Iron Bioavailability of Hummus: Assessment by an In Vitro Digestion/Caco-2 Cell Model

Nour Doumani , Isabelle Séverin , Laurence Dahbi , Elias Bou-Maroun , Maya Tueni et al.
Foods, 2020, 9 (4), pp.474-494. ⟨10.3390/foods9040474⟩
Journal articles hal-02551705v1
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In vitro and in silico hormonal activity studies of di-(2-ethylhexyl)terephthalate, a di-(2-ethylhexyl)phthalate substitute used in medical devices, and its metabolites

Nicolas Kambia , Isabelle Séverin , Amaury Farce , Emmanuel Moreau , Laurence Dahbi et al.
Journal of Applied Toxicology, 2019, 39, pp.1043-1056. ⟨10.1002/jat.3792⟩
Journal articles hal-02068658v1
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Innovative Magnetic Nanoparticles for PET/MRI Bimodal Imaging

Guillaume Thomas , Julien Boudon , Lionel Maurizi , Mathieu Moreau , Paul Walker et al.
ACS Omega, 2019, 4 (2), pp.2637-2648. ⟨10.1021/acsomega.8b03283⟩
Journal articles hal-02068644v1

Genotoxic effects of food contact recycled paperboard extracts on two human hepatic cell lines.

Emilie Souton , Isabelle Séverin , Ludovic Le Hegarat , Kevin Hogeveen , Abdulhadi Aljawish et al.
Food additives & contaminants. Part A. Chemistry, analysis, control, exposure & risk assessment, 2018, 35 (1), pp.159-170. ⟨10.1080/19440049.2017.1397774⟩
Journal articles hal-01625970v1

Use of bioassays to assess hazard of food contact material extracts: State of the art

Isabelle Séverin , Emilie Souton , Laurence Dahbi , Marie-Christine Chagnon
Food and Chemical Toxicology, 2017, 105, pp.429-447. ⟨10.1016/j.fct.2017.04.046⟩
Journal articles hal-01560265v1

Synthesis and characterization of chitosan-coated titanate nanotubes: towards a new safe nanocarrier

Fadoua Sallem , Julien Boudon , Olivier Heintz , Isabelle Séverin , Adel Megriche et al.
Dalton Transactions, 2017, 46, pp.15386-15398. ⟨10.1039/c7dt03029k⟩
Journal articles hal-01625668v1
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In vitro toxicity assessment of extracts derived from sol–gel coatings on polycarbonate intended to be used in food contact applications

Isabelle Séverin , Krystelle Lionti , Laurence Dahbi , Catherine Loriot , Bérangère Toury et al.
Food and Chemical Toxicology, 2016, 93, pp.51 - 57. ⟨10.1016/j.fct.2016.04.025⟩
Journal articles hal-01434899v1
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The consequences of physical post-treatments (microwave and electron-beam) on food/packaging interactions: A physicochemical and toxicological approach

Anne-Marie Riquet-Motchidlover , Colette Breysse , Laurence Dahbi , Catherine Loriot , Isabelle Séverin et al.
Food Chemistry, 2016, 199, pp.59-69. ⟨10.1016/j.foodchem.2015.09.034⟩
Journal articles hal-01243319v1

Use of reliable bioassays to detect potential hazard of food contact materials extracts to ensure quality, safety and innovation of paperboards

Emilie Souton , Isabelle Séverin , Marie-Christine Chagnon
Toxicology Letters, 2015, Toxicology Letters, 238 (2, supplément), pp.S1-420
Journal articles hal-03611999v1

In vitro genotoxicity assessment of MTES, GPTES and TEOS, three precursors intended for use in food contact coatings

Krystelle Lionti , Isabelle Séverin , Laurence Dahbi , Bérangère Toury , Marie-Christine Chagnon et al.
Food and Chemical Toxicology, 2014, 65, pp.76-81. ⟨10.1016/j.fct.2013.11.037⟩
Journal articles hal-01962377v1

Effect of sunlight exposure on the release of intentionally and/or non-intentionally added substances from polyethylene terephthalate (PET) bottles into water: Chemical analysis and in vitro toxicity

Cristina Bach , Xavier Dauchy , Isabelle Séverin , Jean-Francois Munoz , Serge Etienne et al.
Food Chemistry, 2014, 162, pp.63-71. ⟨10.1016/j.foodchem.2014.04.020⟩
Journal articles hal-01296979v1

Effect of temperature on the release of intentionally and non-intentionally added substances from polyethylene terephthalate (PET) bottles into water: Chemical analysis and potential toxicity

Cristina Bach , Xavier Dauchy , Isabelle Séverin , Jean-François Munoz , Serge Etienne et al.
Food Chemistry, 2013, 139 (1-4), pp.672 - 680. ⟨10.1016/j.foodchem.2013.01.046⟩
Journal articles anses-01903693v1

Caffeine increases the expression of cystatin SN in human submandibular acinar-like HSG cells

Micheline Dsamou , Martine Morzel , Ludovic Le Corre , Isabelle Séverin , Marie-Christine Chagnon et al.
Archives of Oral Biology, 2013, 58 (10), pp.1511-1516. ⟨10.1016/j.archoralbio.2013.06.005⟩
Journal articles hal-01960219v1

Risk assessment and management–Food contact materials

Isabelle Séverin , Anne-Marie Riquet , Marie-Christine Chagnon
Cahiers de Nutrition et de Diététique, 2011, 46 (2), pp.59-66
Journal articles hal-01962438v1

Cross talk between nuclear receptor ERalpha ET AhR in human hepatoma cell line (HepG2) exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin

Manuela Goettel , Ludovic Le Corre , Isabelle Séverin , Dieter Schrenk , Marie-Christine Chagnon et al.
Toxicology Letters, 2011, Abstracts of the 47th Congress of the European Societies of Toxicology (EUROTOX), 205, pp.S239-S239. ⟨10.1016/j.toxlet.2011.05.817⟩
Journal articles hal-00722931v1

Genotoxic activities of the food contaminant 5-hydroxymethylfurfural using different in vitro bioassays

Isabelle Séverin , Coralie Dumont , Adeline Jondeau-Cabaton , Vanessa Graillot , Marie-Christine Chagnon et al.
Toxicology Letters, 2010, 192 (2), pp.189-194. ⟨10.1016/j.toxlet.2009.10.022⟩
Journal articles hal-00850790v1
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Safety Evaluation of Food contact paper and board using Chemical Tests and in vitro Bioassays-The role of known and unknown substances

Ulla Honkalampi-Hämäläinen , Emma Bradley , Laurence Castle , Isabelle Séverin , Laurence Dahbi et al.
Food Additives and Contaminants, 2010, 27 (03), pp.406-415. ⟨10.1080/19440040903401358⟩
Journal articles hal-00573087v1
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Test procedures for obtaining representative extracts suitable for reliable in vitro toxicity assessment of paper and board intended for food contact.

Emma Bradley , Annalaura Stammati , Mirja Salkinoja-Salonen , Maria A Andersson , Frederique Bertaud et al.
Food Additives and Contaminants, 2009, 27 (02), pp.262-271. ⟨10.1080/02652030903232746⟩
Journal articles hal-00573894v1

Genotoxic and endocrine activities of bis(hydroxyphenyl)methane (bisphenol F) and its derivatives in the HepG2 cell line

Nicolas J. Cabaton , Coralie Dumont , Isabelle Séverin , Elisabeth Perdu , Daniel Zalko et al.
Toxicology, 2009, 255 (1-2), pp.15-24. ⟨10.1016/j.tox.2008.09.024⟩
Journal articles hal-01962644v1

The BIOSAFEPAPER project for in vitro toxicity assessments: preparation, detailed chemical characterisation and testing of extracts from paper and board samples

E.L Bradley , Ulla Honkalampi-Hamalainen , Assi Weber , Maria Andersson , F. Bertaud et al.
Food and Chemical Toxicology, 2008, 46 (7), pp.2498-2509. ⟨10.1016/j.fct.2008.04.017⟩
Journal articles hal-01982280v1

Toxicological profile of cereulide, the Bacillus cereus emetic toxin, in functional assays with human, animal and bacterial cells

Maria Andersson , Pasi Hakulinen , Ulla Honkalampi-Hamalainen , Douwe Hoornstra , Jean-Claude Lhuguenot et al.
Toxicon, 2007, 49 (3), pp.351-367. ⟨10.1016/j.toxicon.2006.10.006⟩
Journal articles hal-01977773v1

Safety assessment of food-contact paper and board using a battery of short-term toxicity tests: European union BIOSAFEPAPER project

Isabelle Séverin , Jean-Claude Lhuguenot , Maria A Andersson , Douwe Hoornstra , Mirja Salkinoja-Salonen et al.
Food additives and contaminants, 2005, 22 (10), pp.1032-1041. ⟨10.1080/02652030500183425⟩
Journal articles hal-01977840v1

2,4-Diaminotoluene (2,4-DAT)-induced DNA damage, DNA repair and micronucleus formation in the human hepatoma cell line HepG2

Isabelle Séverin , Adeline Jondeau , Laurence Dahbi , Marie-Christine Chagnon
Toxicology, 2005, 213 (1-2), pp.138-146. ⟨10.1016/j.tox.2005.05.021⟩
Journal articles hal-01981435v1

The autoradiographic test for unscheduled DNA synthesis : a sensitive assay for the detection of DNA repair in the HepG2 cell line

Isabelle Valentin-Severin , V. Thybaud , A.M. Lebon , J.C. Lhuguenot , Marie-Christine Chagnon et al.
Mutation Research - Genetic Toxicology and Environmental Mutagenesis, 2004, 559, pp.211-217
Journal articles hal-02672058v1

The autoradiographic test for unscheduled DNA synthesis: a sensitive assay for the detection of DNA repair in the HepG2 cell line

Isabelle Valentin-Severin , Véronique Thybaud , Anne-Marie Le Bon , Jean-Claude Lhuguenot , Marie-Christine Chagnon et al.
Mutation Research - Genetic Toxicology and Environmental Mutagenesis, 2004, 559 (1-2), pp.211-217. ⟨10.1016/j.mrgentox.2003.12.007⟩
Journal articles hal-01981453v1

Use of HepG2 cell line for direct or indirect mutagens screening: comparative investigation between comet and micronucleus assays.

Isabelle Valentin-Severin , Ludovic Le Hegarat , Jean-Claude Lhuguenot , Anne-Marie Le Bon , Marie-Christine Chagnon et al.
Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis, 2003, 536 (1-2), pp.79-90. ⟨10.1016/S1383-5718(03)00031-7⟩
Journal articles hal-01981654v1

Toxic interaction between hydroxyurea and 1-beta-D-arabino-furanosylcytosine on the DNA of a human hepatoma cell line (HEPG2).

Isabelle Séverin , Martine Padieu , Jean-Claude Lhuguenot , Marie-Christine Chagnon
Toxicology Letters, 2003, 145 (3), pp.303-11. ⟨10.1016/j.toxlet.2003.08.003⟩
Journal articles hal-01981468v1

Use of HepG2 cell line for direct or indirect mutagens screening : comparative investigation between comet and micronucleus assays

Isabelle Valentin-Severin , L. Le Hagarat , J.C. Lhuguenot , A.M. Lebon , Marie-Christine Chagnon et al.
Mutation Research - Genetic Toxicology and Environmental Mutagenesis, 2003, 536, pp.79-90
Journal articles hal-02680011v1

Uridine uptake inhibition assay: an automated micromethod for the screening of cytotoxicity.

Isabelle Valentin-Severin , Laurence Laignelet , Jean Claude Lhuguenot , Marie-Christine Chagnon
Toxicology, 2002, 171 (2-3), pp.207-13. ⟨10.1016/S0300-483X(01)00587-X⟩
Journal articles hal-01981698v1
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Uridine uptake inhibition as a cytotoxicity test for a human hepatoma cell line (HepG2 cells): comparison with the neutral red assay

Isabelle Valentin , Murielle Philippe , Jean-Claude Lhuguenot , Marie-Christine Chagnon
Toxicology, 2001, 158, pp.127-139
Journal articles hal-01981819v1

Metabolism of N-butyl benzyl phtalate in the female wistar rat. Identification of new metabolites

C. Nativelle , K. Picard , Isabelle Valentin , J.C. Lhuguenot , Marie-Christine Chagnon et al.
Food and Chemical Toxicology, 1999, 37, pp.905-917
Journal articles hal-02694753v1
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Metabolism of N-Butyl Benzyl Phthalate in the Female Wistar Rat. Identification of New Metabolites

C Nativelle , K Picard , Isabelle Valentin , Jean-Claude C Lhuguenot , Marie-Christine Chagnon et al.
Food and Chemical Toxicology, 1999, 37, pp.905-917
Journal articles hal-01981781v1

P22-05 Identification and hazard assessment of oligoesters, nonintentionally added substances present in food contact coating extracts

Ruzanna Hayrapetyan , Isabelle Séverin , V. Monneraye , R. Cariou , Marie-Christine Chagnon et al.
16th International Congress of Toxicology (ICT) - Uniting in Toxicology, Sep 2022, Maastricht, Netherlands. pp.S271-S271, ⟨10.1016/j.toxlet.2022.07.719⟩
Conference papers hal-03948279v1

Effects of genistein, vinclozolin and BPA on the proliferation and differentiation of a human salivary cell line – CIME project

Laurence Dhabi , Isabelle Séverin , Marie-Chantal Canivenc-Lavier , Marie-Christine Chagnon
Colloque PNR-PE , Dec 2012, Paris, France. 1 p
Conference papers hal-01594399v1

Food contact materials: Strategy for quality and food safety of packaging systems

Isabelle Séverin , Laurence Dahbi , Catherine Bergès , Coralie Dumont , Marie-Christine Chagnon et al.
47. Congress of the European-Societies-of-Toxicology, Aug 2011, Paris, France. 2 p., ⟨10.1016/j.toxlet.2011.05.732⟩
Conference papers hal-02749456v1

Identification of genotoxic and endocrine disruption activities of 4,4’-dihydroxydiphenyl-methane (BPF) and its metabolites using human cell lines

N J Cabaton , Coralie Dumont , Isabelle Séverin , Daniel Zalko , Marie-Christine Chagnon et al.
Congrès Annuel de la Société Française de toxicologie, Oct 2007, Montpellier, France
Conference papers hal-03593237v1

Use of bcl2 stably transfected HepG2 cell line to improve the specificity of the comet assay

Isabelle Séverin , Marie-Odile Eichler , Laurence Dahbi , Marie-Christine Chagnon
Molecular Research in Environmental Medicine, 2. international conference, Sep 2006, Paris, France
Conference papers hal-03592899v1
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Could CTA be a reliable alternative method to identify non-genotoxic substances in Food Contact Material extract ?

Théo Lacour , Ruzanna Hayrapetyan , Isabelle Séverin , Isabelle Mouche , Francis Finot et al.
ICT 2022 The XVIth International Congress of Toxicology, Sep 2022, Maastricht, Netherlands. , 368, pp.S141, 2022, ⟨10.1016/j.toxlet.2022.07.402⟩
Conference poster hal-03819008v1
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Lebanese pita extracts with presence of trace elements: hazard assessment

Isabelle Séverin , Elias Bou-Maroun , Rita Akiki , Ghiwa Zoghbi , Nada Lebbos et al.
47th Meeting of the European Environmental Mutagenesis and Genomics Society (EEMGS), May 2019, Rennes, France. ⟨10.13140/RG.2.2.30583.88489⟩
Conference poster hal-02296298v1
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Extraction d'éléments traces métalliques à partir de pains libanais et évaluation du danger de ces mélanges

Isabelle Séverin , N. Lebbos , Elias Bou-Maroun , C. Daou , R. Ouaini et al.
SFT 2018, 2018, Dijon, France
Conference poster hal-01986057v1
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In vitro hazard assessment of nanoparticles developed for biomedical applications

Annette Luce , Y Saibi , Isabelle Séverin , Julien Boudon , Nadine Millot et al.
European Society of Toxicology In Vitro (ESTIV) 2016 meeting, Oct 2016, Juan-les-Pins, France. 2016
Conference poster hal-01986190v1
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Reliable bioassays to detect potential hazard of paperboard food contact material extracts

Emilie Souton , Laurence Dahbi , Thomas Nury , Abdulhadi Aljawish , Isabelle Séverin et al.
European Society of Toxicology In Vitro (ESTIV) 2016 meeting, Oct 2016, Juan-les-Pins, France. 2016
Conference poster hal-01989751v1
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Genotoxicity assessment of a polycarbonate sol-gel coating and its precursors intended to be used for food contact

Isabelle Séverin , K. Lionti , Laurence Dahbi , C. Loriot , Bérangère Toury et al.
2016 ILSI Annual Meeting, Jan 2016, St. Petersburg, Fl, United States.
Conference poster hal-01989582v1
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Use of reliable bioassays to detect potential hazard of food contact materials extracts to ensure quality, safety and innovation of paperboards

Emilie Souton , Isabelle Séverin , Marie-Christine Chagnon
51st Congress of the European Societies of Toxicology (EUROTOX), Sep 2015, Porto, Portugal. 51st Congress of the European Societies of Toxicology (EUROTOX), 238 (2, supplément), pp.S348, 2015, Toxicology Letters
Conference poster hal-01985967v1
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Salivary proteome and sensitivity to bitterness

Micheline Dsamou , Olivier Palicki , Chantal Septier , Isabelle Séverin , Marie-Christine Chagnon et al.
5. Congrès international goût-nutrition-santé, Mar 2010, Dijon, France. 1 p., 2010
Conference poster hal-01137080v1

Effects of estradiol on TCDD-induced oxidative stress in hepatoma cells

Manuela Goettel , Isabelle Séverin , Marie-Christine Chagnon , Dieter Schrenk
44. Congress of the European Societies of Toxicology, 2007/10/7-10, 2007, Amsterdam, Netherlands. , 2007, ⟨10.1016/j.toxlet.2007.05.578⟩
Conference poster hal-02821345v1

Packaging

Isabelle Séverin , Hervé Lonque
Gases in Agro-Food Processes, Academic Press, pp.335-362, inPress, 9780128124659
Book sections hal-02499160v1

Chapter 7. Food Processing

Isabelle Séverin , Hervé Lonque
Gases in Agro-Food Processes, Academic Press, pp.680, inPress, 9780128124659
Book sections hal-01984636v1

Principes généraux d'évaluation/gestion du risque des matériaux au contact des denrées alimentaires

Isabelle Séverin , R. Serafimova , G. Kass , Marie-Christine Chagnon
Pathologie professionnelle et de l'environnement, 1470 p., 2017, 9782842995355
Book sections hal-01984541v1

EU régulations and general principles

Isabelle Séverin , Marie-Christine Chagnon
Bioactivators in food, Kontaminas Mickael, pp.442-455, 2015
Book sections hal-01961954v1