Investigation and risk evaluation of the occurrence of carbamazepine, oxcarbazepine, their human metabolites and transformation products in the urban water cycle.

Trace organic contaminants such as pharmaceuticals, personal care products and industrial chemicals are frequently detected in the urban water cycle, including wastewater, surface water and groundwater, as well as drinking water. These also include human metabolites (HMs), which are formed in the human body and then excreted via urine or feces, as well as transformation products (TPs) formed in engineered treatment systems and the aquatic environment. In the current study, the occurrence of HMs as well as their TPs of the anticonvulsants carbamazepine (CBZ) and oxcarbazepine (OXC) were investigated using LC tandem MS in effluents of wastewater treatment plants (WWTPs), surface water and groundwater. Highest concentrations were observed in raw wastewater for 10,11-dihydro-10,11-dihydroxycarbamazepine (DiOHCBZ), 10,11-dihydro-10-hydroxy-cabamazepine (10OHCBZ) and CBZ with concentrations ranging up to 2.7 ± 0.4, 1.7 ± 0.2 and 1.07 ± 0.06 µg L-1, respectively. Predictions of different toxicity endpoints using a Distributed Structure-Searchable Toxicity (DSSTox) expert system query indicated that several HMs and TPs, in particular 9-carboxy-acridine (9-CA-ADIN) and acridone (ADON), may exhibit an increased genotoxicity compared to the parent compound CBZ. As 9-CA-ADIN was also detected in groundwater, a detailed investigation of the genotoxicity of 9-CA-ADIN is warranted. Investigations of an advanced wastewater treatment plant further revealed that the discharge of the investigated compounds into the aquatic environment could be substantially reduced by ozonation followed by granular activated carbon (GAC) filtration.

Why Small Differences Matter: Elucidation of the Mechanisms Underlying the Transformation of 2OH- and 3OH-Carbamazepine in Contact with Sand Filter Material.

Carbamazepine (CBZ) is a worldwide used antiepileptic drug, which is metabolized to a large extent in the human body to several metabolites, including 10,11-dihydroxy-10,11-dihydrocarbamazepine (DiOHCBZ), 2-hydroxycarbamazepine (2OHCBZ), and 3-hydroxycarbamazepine (3OHCBZ). 2OHCBZ and 3OHCBZ were previously detected in raw and treated wastewater revealing their widespread emission into the aquatic environment, eventually leading to the contamination of drinking water resources. Sand filtration is frequently applied in drinking water treatment for the removal of inorganic species and suspended particles but has been shown to be capable of removing trace organic contaminants. This study focuses on the elucidation of the (bio)transformation mechanisms of 2OHCBZ and 3OHCBZ in contact with material taken from a rapid sand filter of a German waterworks. Despite their similar structure, which differs only in the position of the phenolic OH moiety, both compounds underwent distinct transformation reactions leading to the formation of a variety of transformation products (TPs). The main biochemical reactions thereby included enzymatic transformation of 2OHCBZ resulting in the formation of a reactive iminoquinone intermediate (2OHCBZ) and nitration via peroxynitrite (2OHCBZ and 3OHCBZ) as well as formation of radicals leading to dimerization (3OHCBZ). Further transformation reactions included hydroxylation, ring cleavage, loss of carbamoyl group, and decarboxylation, as well as O-methylation.