Denatonium, torasemide and their transformation products as emerging contaminants in the aquatic environment

Abstract

The work conducted for this thesis closes knowledge gaps in the context of denatonium, torasemide, and their transformation products as environmental pollutants.

Denatonium is one of the bitterest compounds known today, and it is applied in numerous products to prevent an accidental or intentional consumption. Despite its wide application, this is the first study reporting denatonium itself as environmental pollutant. Generally, all water samples taken from WWTP effluents in Italy, Switzerland and from 22 plants in the federal state of Baden-Württemberg, Germany, contained denatonium with a maximum concentration of 341 ng/L. Denatonium is not significantly removed during conventional wastewater treatment and concentrations up to almost 200 ng/L were detected in wastewater-impacted surface waters. When ozonation is applied as advanced treatment technique, up to 74% of an initial denatonium load could be removed from wastewater. However, removal of denatonium was associated here by the formation of at least two polar transformation products (TPs) with unknown toxicological properties. Denatonium can undergo indirect photodegradation and seven TPs were identified for this process. They formed via amide hydrolysis, hydroxylation, N-dealkylation, and N-dearylation. Lidocaine was however the only TP of denatonium detected after conventional wastewater treatment and in surface waters, but the occurrence of this compound was associated with its application as local anesthetic rather than being a degradation product of denatonium. Generally, data presented previously in literature and the results obtained in this study point towards a persistent nature of denatonium and therefore an accumulation of this compound in the environment.

Torasemide is an important loop diuretic and it was 2017 one of the ten most prescribed drugs in Germany. Maximum concentrations of this drug measured in this study for WWTPs and surface waters were about 350 ng/L and 70 ng/L, respectively. Despite an already known occurrence of torasemide throughout the urban water cycle, including very low concentrations in drinking water, no studies were performed related to its fate in the environment and an occurrence of TPs so far. Abiotic and biotic degradation experiments were therefore performed and overall sixteen products were identified. The following reaction mechanisms were involved in TP formation: aromatic and aliphatic hydroxylation, including further oxidation to carboxylic acids and quinone imines, amide cleavage, N-dealkylation, N-dearylation, and sulfonamide hydrolysis to sulfonic acids. The formation of quinone imines was in principle of great interest due to their highly reactive nature, but they were not detected in any environmental sample. While both major human metabolites hydroxytorasemide and carboxytorasemide were observed in WWTP influents, hydroxytorasemide seems to be removed during wastewater treatment and was most likely transformed into carboxytorasemide. Carboxytorasemide however was detected in all investigated WWTP effluents and surface waters, with an estimated maximum concentration of 1 µg/L.