Microbial biotransformation of furosemide for environmental risk assessment: identification of metabolites and toxicological evaluation.

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.

A coupled Bio-EF process for mineralization of the pharmaceuticals furosemide and ranitidine: Feasibility assessment.

A coupled Bio-EF treatment has been applied as a reliable process for the degradation of the pharmaceuticals furosemide (FRSM) and ranitidine (RNTD) in aqueous medium, in order to reduce the high energy consumption related to electrochemical technology. In the first stage of this study, electrochemical degradation of the drugs was assessed by the electro-Fenton process (EF) using a BDD/carbon-felt cell. Biodegradability of the drugs solutions was enhanced reaching BOD5/COD ratios close to the biodegradability threshold of 0.4, evidencing the formation of bio-compatible by-products (mainly short-chain carboxylic acids) which are suitable for biological post-treatment. Moreover, toxicity evaluation by the Microtox(®) method revealed that EF pre-treatment was able of detoxifying both, FRSM and RNTD solutions, constituting another indicator of biodegradability of EF treated solutions. In the second stage, electrolyzed solutions were treated by means of an aerobic biological process. A significant part of the short-chain carboxylic acids formed during the electrochemical phase was satisfactorily removed by the used selected microorganisms. The results obtained demonstrate the efficiency and feasibility of the integrated Bio-EF process.

Pyrite as a sustainable catalyst in electro-Fenton process for improving oxidation of sulfamethazine. Kinetics, mechanism and toxicity assessment.

The degradation of 0.20 mM sulfamethazine (SMT) solutions was investigated by heterogeneous electro-Fenton (EF) process using pyrite as source of Fe(2+) (catalyst) and pH regulator in an undivided electrochemical cell equipped either with a Pt or a BDD anode and carbon-felt as cathode. Effect of pyrite concentration and applied current on the oxidative degradation kinetics and mineralization efficiency has been studied. The higher oxidation power of the process, named "Pyrite-EF″ using BDD anode was demonstrated. Pyrite-EF showed a better performance for the oxidation/mineralization of the drug SMT in comparison to the classic EF process: 95% and 87% TOC removal by Pyrite-EF with BDD and Pt anodes, respectively, versus 90% and 83% by classical EF with BDD and Pt anodes, respectively. The rate constant of the oxidation of SMT by OH was determined by the competition kinetics method and found to be 1.87 × 10(9) mol(-1) L s(-1). Based on the identified reaction intermediates by HPLC and GS-MS, as well as released SO4(2-), NH4(+) and NO3(-) ions, a plausible reaction pathway was proposed for the mineralization of SMT during Pyrite-EF process. Toxicity assessment by means of Microtox method revealed the formation of some toxic intermediates during the treatment. However, toxicity of the solution was removed at the end of treatment.