title: Microbial biotransformation of furosemide for environmental risk assessment: identification of metabolites and toxicological evaluation.
abstract: Some widely prescribed drugs are sparsely metabolized and end up in the environment. They can thus be a focal point of ecotoxicity, either themselves or their environmental transformation products. In this context, we present a study concerning furosemide, a diuretic, which is mainly excreted unchanged. We investigated its biotransformation by two environmental fungi, Aspergillus candidus and Cunninghamella echinulata. The assessment of its ecotoxicity and that of its metabolites was performed using the Microtox test (ISO 11348-3) with Vibrio fischeri marine bacteria. Three metabolites were identified by means of HPLC-MS and1H/13C NMR analysis: saluamine, a known pyridinium derivative and a hydroxy-ketone product, the latter having not been previously described. This hydroxy-ketone metabolite was obtained with C. echinulata and was further slowly transformed into saluamine. The pyridinium derivative was obtained in low amount with both strains. Metabolites, excepting saluamine, exhibited higher toxicity than furosemide, being the pyridinium structure the one with the most elevated toxic levels (EC50= 34.40 ± 6.84 mg L-1). These results demonstrate that biotic environmental transformation products may present a higher environmental risk than the starting drug, hence highlighting the importance of boosting toxicological risk assessment related to the impact of pharmaceutical waste.
authors: Laboratoire Molécules de Communication et Adaptation des Microorganismes (MCAM), UMR 7245 CNRS-MNHN, Muséum national d'Histoire naturelle, CNRS, Sorbonne Universités, CP 54, 57 rue Cuvier, 75005, Paris, France.|Laboratoire Géomatériaux et Environnement (LGE), Université Paris-Est, EA 4508, UPEM, 77454, Marne-la-Vallée, France.
authors: Hugo
authors: H
authors: Olvera-Vargas
authors: Laboratoire Molécules de Communication et Adaptation des Microorganismes (MCAM), UMR 7245 CNRS-MNHN, Muséum national d'Histoire naturelle, CNRS, Sorbonne Universités, CP 54, 57 rue Cuvier, 75005, Paris, France.
authors: Sébastien
authors: S
authors: Leroy
authors: Institut de Chimie et des Matériaux de Paris-Est, UMR CNRS UPEC 7182, Université Paris-Est, 94320, Thiais, France.
authors: Michael
authors: M
authors: Rivard
authors: Laboratoire Géomatériaux et Environnement (LGE), Université Paris-Est, EA 4508, UPEM, 77454, Marne-la-Vallée, France.
authors: Nihal
authors: N
authors: Oturan
authors: Laboratoire Géomatériaux et Environnement (LGE), Université Paris-Est, EA 4508, UPEM, 77454, Marne-la-Vallée, France.
authors: Mehmet
authors: M
authors: Oturan
authors: Laboratoire Molécules de Communication et Adaptation des Microorganismes (MCAM), UMR 7245 CNRS-MNHN, Muséum national d'Histoire naturelle, CNRS, Sorbonne Universités, CP 54, 57 rue Cuvier, 75005, Paris, France. buisson@mnhn.fr.
authors: Didier
authors: http://orcid.org/0000-0001-8323-386X
authors: D
authors: Buisson
mesh_terms: D001230:Aspergillus / Q000378:metabolism*; D001673:Biodegradation, Environmental; D001711:Biotransformation; D020093:Cunninghamella / Q000378:metabolism*; D005665:Furosemide / Q000737:chemistry / Q000378:metabolism*; D013058:Mass Spectrometry; D018570:Risk Assessment; D014874:Water Pollutants, Chemical / Q000737:chemistry / Q000378:metabolism*
chemical_list: D014874:Water Pollutants, Chemical; D005665:Furosemide
keywords: Biodegradation; Degradation pathway; Ecotoxicology; Environmental transformation products; Oxidation