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Vers le développement de composés pharmaceutiques durables : Caractérisation de la dégradation et évaluation écotoxicologique d’un analogue d'anticancéreux eco-conçu

Abstract : Pharmaceuticals are increasingly reported to contaminate natural waters because of their partial elimination by wastewater treatment plant and can have an impact on aquatic organisms up to human health through potable water in the case of the most persistent ones. Additionally, their transformation products (TPs) are often unidentified and their impacts are insufficiently assessed.To limit this contamination, one promising lever is the ecoconception, considering environmental fate and impact since the development of the molecule design. An eco-designed molecule would then be a molecule which degrades easily and which would produce harmless TPs once excreted in the environment.The validity of this innovative approach was assessed using the cytotoxic methotrexate (MTX) as drug model, due to its potent action, its reported presence in wastewater effluent and its ability to produce a harmful metabolite (7-hydroxy-methotrexate), comparing to an analog (OMTX) synthesized with the hypothesis it will be less persistent and produce less toxic TPs. This hypothesis was assessed through i) photodegradation studies where 11 TPs were evidenced for MTX and 12 for OMTX, revealing similar degradation pathways but faster degradation kinetics under 254 nm for OMTX; ii) a biodegradation study by an activated sludge where no major effects were observed on the microbial community. 8 additional TPs were evidenced for MTX, the harmful 7-hydroxy-mehtotrexate was found minor and transient, and 4 TPs for OMTX which was biodegraded faster; iii) cytotoxicity tests conducted during photo and biodegradation indicating TPs lost the original pharmaceutical action and finally iv) an acute aquatic ecotoxicological assessment in favor of OMTX
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https://pastel.archives-ouvertes.fr/tel-03710362
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Submitted on : Thursday, June 30, 2022 - 3:48:36 PM
Last modification on : Friday, August 5, 2022 - 2:41:12 PM

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  • HAL Id : tel-03710362, version 1

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Anaïs Espinosa. Vers le développement de composés pharmaceutiques durables : Caractérisation de la dégradation et évaluation écotoxicologique d’un analogue d'anticancéreux eco-conçu. Ecologie, Environnement. AgroParisTech, 2022. Français. ⟨NNT : 2022AGPT0004⟩. ⟨tel-03710362⟩

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