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 and 1H/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.
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The authors wish to thank S. Amand for technical assistance, L. Dubost for mass spectra and A. Deville for NMR spectra.
Conflict of interest
The authors declare that they have no conflict of interest.
This article does not contain any studies with human participants or animals performed by any of the authors.
This study was funded by the European Commission through the Erasmus Mundus Joint Doctorate Programme (Environmental Technologies for Contaminated Solids, Soils and Sediments) (grant number FPA n°2010–0009), and CONACyT, Mexico.
Responsible editor: Philippe Garrigues
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Olvera-Vargas, H., Leroy, S., Rivard, M. et al. Microbial biotransformation of furosemide for environmental risk assessment: identification of metabolites and toxicological evaluation. Environ Sci Pollut Res 23, 22691–22700 (2016). https://doi.org/10.1007/s11356-016-7398-2
- Degradation pathway
- Environmental transformation products