Development of a novel universal proxy to assess the environmental fate and impact of complex (bio)pesticides by Mass Spectrometry-based Metabolomics Hikmat Ghosson To cite this version: Hikmat Ghosson. Development of a novel universal proxy to assess the environmental fate and im- pact of complex (bio)pesticides by Mass Spectrometry-based Metabolomics. Analytical chemistry. Université de Perpignan, 2020. English. NNT : 2020PERP0029. tel-03155733 HAL Id: tel-03155733 https://tel.archives-ouvertes.fr/tel-03155733 Submitted on 2 Mar 2021 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Délivré par UNIVERSITE DE PERPIGNAN VIA DOMITIA Préparée au sein de l’école doctorale ED 305 Energie et Environnement Et de l’unité de recherche USR 3278 – CRIOBE – EPHE-CNRS-UPVD Spécialité : Chimie Analytique Présentée par Hikmat GHOSSON TITRE DE LA THESE Développement d’un nouveau proxy universel pour évaluer le devenir et l’impact environnemental de (bio)pesticides complexes par Métabolomique basée sur la Spectrométrie de Masse Soutenue le 04/12/2020 devant le jury composé de Mme. Carole CALAS-BLANCHARD, Professeur des Universités Président Université de Perpignan Via Domitia Mme. Emmanuelle VULLIET, Directeur de recherche, H.D.R. Rapporteur Centre National de la Recherche Scientifique M. Laurent DEBRAUWER, Ingénieur de recherche, H.D.R. Rapporteur Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement M. Julien BOCCARD, Collaborateur scientifique Examinateur Université de Genève M. Yann GUITTON, Ingénieur de recherche Examinateur École Nationale Vétérinaire, Agroalimentaire et de l'Alimentation, Nantes-Atlantique M. Cédric BERTRAND, Professeur des Universités Directeur de thèse Université de Perpignan Via Domitia Mme. Marie-Virginie SALVIA, Maître de conférences, H.D.R. Co-directeur Université de Perpignan Via Domitia A Thesis submitted for the degree of Doctor of Philosophy Delivered by UNIVERSITE DE PERPIGNAN VIA DOMITIA Prepared at the doctoral school ED 305 Energie et Environnement And the research unit USR 3278 – CRIOBE – EPHE-CNRS-UPVD Major Analytical Chemistry By Hikmat GHOSSON THESIS TITLE Development of a novel universal proxy to assess the environmental fate and impact of complex (bio)pesticides by Mass Spectrometry-based Metabolomics Defended on December 04, 2020 before the jury composed of Mme. Carole CALAS-BLANCHARD, Professeur des Universités President Université de Perpignan Via Domitia Mme. Emmanuelle VULLIET, Directeur de recherche, H.D.R. Rapporteur Centre National de la Recherche Scientifique M. Laurent DEBRAUWER, Ingénieur de recherche, H.D.R. Rapporteur Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement M. Julien BOCCARD, Collaborateur scientifique Examiner Université de Genève M. Yann GUITTON, Ingénieur de recherche Examiner École Nationale Vétérinaire, Agroalimentaire et de l'Alimentation, Nantes-Atlantique M. Cédric BERTRAND, Professeur des Universités Thesis Director Université de Perpignan Via Domitia Mme. Marie-Virginie SALVIA, Maître de conférences, H.D.R. Co-director Université de Perpignan Via Domitia Dedication To those who sacrificed their lives when struggling for the foundation of the Lebanese National University… “Aut viam inveniam aut faciam” “We will either find a way, or make one” Hannibal Barca, the Canaanite Commander of Carthage Acknowledgments I would like to thank every person who contributed, supported, or helped realizing the present work and fulfilling the missions required for achieving the present dissertation, and I apologize in advance to any single person who I may forget to mention… You were many, colleagues and friends, to participate in this experience and I am very grateful to you and to your appreciated efforts and support. First, I would like to acknowledge the members of the Jury Dr. Emmanuelle VULLIET and Dr. Laurent DEBRAUWER, to have given me the honor of being the Rapporteurs of this dissertation, and to have given their precious time to read and assess of the present manuscript. I also acknowledge Pr. Carole CALAS-BLANCHARD, Dr. Yann GUITTON and Dr. Julien BOCCARD for their acceptance to examine the present work and to participate in the Jury of my thesis. This is a great honor for me. I would like to express my gratitude for the two persons who gave me the opportunity to access this distinct experience, and supervised my work during those three years. They let me take the initiative, helped me focusing the targets, and were always open to discuss new ideas and propositions… And despite all the difficulties and the critical moments, they always supported my work by transferring their knowledge and experience to me, which improved my scientific, technical and personal skills and maturity. They gave me their trust, and finally guided me towards the accomplishment of this dissertation with a lot of satisfaction from my part, so I am very grateful for them, and I had the pleasure to work under their guidance, and still… Thus, I express my deepest thanks to my supervisors Pr. Cédric BERTRAND and Dr. Marie-Virginie SALVIA. I would like express my deepest recognition to Dr. Frédérique COURANT, Dr. Anne-Emmanuelle HAY-DE BETTIGNIES, Pr. Thierry NOGUER, and once again, Dr. Yann GUITTON for their acceptance to guide and participate in my “Comité de Suivi Individuel” (CSI), and for their appreciated support, guidance and advices that helped me achieving my targets and orientating my future perspectives. I acknowledge the Doctoral School “ED 305”, represented by Pr. Nicolas INGUIMBERT, the Doctoral School Director, and the Doctoral School Council represented by all its members, for granting me the doctoral fellowship, and for supporting the pursuit of my learning cursus and training activities. I also acknowledge the “Réseau Francophone de Métabolomique et Fluxomique” (RFMF), and the “Société Française de Spectrométrie de Masse” (SFSM) for the grants that they afforded to me during the three years of the doctoral work, and for allowing me to participate and communicate in the workshops, the schools and the congresses that they organized. These participations helped me improving my knowledge, my skills and my network that were necessary for the accomplishing of the present thesis, and for my aimed future career in scientific research as well. I would like to express my acknowledgments to all the collaborators who were involved in all or parts of the present thesis. They will be mentioned in the subsequent chapters of the present manuscript. I express all my sincere gladness to have worked with the CRIOBE team, so I thank all the former and actual “Criobian” colleagues, without any exception, for being a graceful part from this experience. I express my special amical gratitude for my colleagues Chandra, Mathieu, Amani, Slimane, Mélina, Mélanie, Laurine, Christian, and Christelle, for the great time that we spent together when trying to “joyfully” struggle with our theses and research topics. Also, my special thanks to Delphine, Jennifer and Peter who were always here to help and afford their great support. Otherwise, I would like to express my heartfelt thanks to my former supervisors and teachers Dr. Nicolas LE YONDRE, Dr. Adrián SCHWARZENBERG and Dr. Wafaa NOUN for teaching me and for encouraging my will to take this distinct challenge, and for their permanent and precious support before and during those three years. They always afforded a great help for me, especially when I faced many difficult moments and obstacles, and they have never stopped dedicating their time, their support and their knowledge whenever I asked. I also warmly thank my friend-colleague Dr. Rim JABER, for affording her great help and precious time when I was preparing for the doctoral entrance exam and for all the professional and personal advices that she gave me along those three years. I am very grateful and should acknowledge my teachers Mr. Imad DIB, Mr. Rami ABOU SAMRA, Mr. Joseph HLEIHEL, Mr. Naji MAKHOUL, Mrs. Maria KAZZI and Mrs. Rola ATALLAH for baptizing my early passion in Science. I also acknowledge their essential role in teaching me how to assume my responsibilities and how to respect my professional, social and personal duties. I was and will be always honored for being one of your students… My deepest acknowledgments to my friends-colleagues Dr. Ihsan EL MASRI, Dr. Mohamad EL MAOUCH, Dr. May TAHA, Dr. Ali EL ZEIN, Dr. Racha ZGHEIB and Dr. Jamal EL HACHEM for their encouragement and permanent support before and during those three years. My warmest thanks to the dearest Mira, my classmate-partner, my colleague, and my great friend who was always here to encourage me, and for being the person who understood the most my difficulties, as well as my gladness, my perspectives and my ambitions. My distinct thanks to Sara, for always being here, especially during those last and most difficult moments. You were a great unforgettable support. I owe you one so when you will make your decision and take your way towards your own adventure, be sure, I will be there… And last but not least, all my profound, warm, and grateful thanks to my small family… Maha, Ibrahim, Samar and Ward.. No words can express my gratitude to you… Your ultimate confidence and infinite support were and will be always the reason why I can overcome difficulties, achieve success, and aim beyond… Résumé Malgré la prise de conscience écologique et sanitaire, la consommation mondiale des pesticides est en augmentation. Étant donné que ces produits chimiques présentent de nombreux effets néfastes sur la santé humaine et l'environnement, des mesures doivent être prises afin de limiter leurs effets.