## 2 Contaminants of Emerging Concern (CECs)
### Pharmaceuticals (PhACs)
Substances found in fewer reports, but at very high concentrations were norepinephrine (2633 ng/L in Dniester River), fluconazole (3390 ng/L in Dniester River) [26], and furosemide (444.63 ng/L in the Mures, River) [51]. Considering the studies on the Lower Danube River basin, the concentration of frequently monitored compounds in the surface water ranged as follows: carbamazepine 3.94-945 ng/L; diclofenac 0.8-255 ng/L; sulfamethoxazole 30-204 ng/L; trimethoprim 0.8-223 ng/L; ibuprofen 3.32-346 ng/L (Figure 2). Concentrations exceeding--EQS of carbamazepine, sulfamethoxazole, trimethoprim, diclofenac, and erythromycincin were found in the Danube tributaries such as Morava river [38], Arges river [10; 44; 49], Mures river [51], and Jijia river [53], in sites that are heavily impacted by municipal or industrial wastewater discharges. Thus, the highest concentrations of carbamazepine (945 ng/L), sulfamethoxazole (204 ng/L) and diclofenac (255 ng/L) were reported in the Arges River, highly affected by the municipal and industrial discharges of the capital of Romania, the city of Bucharest. The concentration measured in the Danube River for the pharmaceuticals mentioned in the \"Watch lists\" [36; 37] were below EQS. Comparing with data on other river in Europe, including the upper Danube, concentrations of carbamazepine of 559 ng/L were reported in River Fyrisan (Sweden), 490 ng/L in river Grundlach (Germany), and 1670 ng/L in Ebro basin (Spain) [54]. High concentration of diclofenac of 930 ng/L was previously reported in upper Danube (Budapest, Hungary, September 2008) [55]. Sulfamethoxazole concentrations of 540 ng/L in surface water were recently reported in the upper Danube catchment area in Croatia [56]. However, the PhACs carbamazepine, diclofenac, and amoxicillin were previously listed as Danube basin-specific pollutants, derived within the EU-project SOLUTIONS [57]. Figure 2: Variation of common pharmaceuticals in surface waters of Lower Danube basin compared to the proposed EQS, according to the Decisions 2018/840/EU and 2020/1161/EU. Caffeine is also present in the Lower Danube and tributary waters. Both minimum (5.27 ng/L [47] and maximum concentrations (306 ng/L [46]) were reported along the Danube River near Novi Sad in two different studies. As this compound is efficiently removed by wastewater treatment plants, caffeine is a suitable marker of the presence of untreated wastewater. JDS3 reported a median concentration of caffeine of 93 ng/L in the Danube and 123 ng/L in the tributary [58]. Very high PhACs concentration was reported in the Dniester River (transboundary river between Ukraine and the Republic of Moldova) in a recent wide-scope screening study by [PERSON] et al. [26]. In total, 40 PhACs compounds and their metabolites were determined in surface water samples. The highest total cumulative PhACs concentration was 26.1 ug/L (a total of 35 contaminants) in a site receiving wastewaters from Chisinau town and the pharmaceutical industry. A concentration of carbamazepine of 1981 ng/L (more than double that the maximum concentration reported in Arges River) and 2858 ng/L for carbamazepine metabolite was reported in Byk River, Moldova [26]. Fluconazole concentration of 3390 ng/L and sulfamethoxazole of 1290 ng/L were measured for the same sampling site. Additionally, metabolites such as 4-acetamidoantipyrine (maximum concentration of 1611 ng/L) and 10,11-dihydro-10,11-dihydroxycarbamazepine (2858 ng/L) were detected in a higher concentration than the parent compounds [26], a fact that has been reported to occur in wastewater samples [51], and demonstrates the impact of uncontrolled discharge. Compared to Dniester, in the transboundary Prut River (Romania and Moldova), 4-acetamidantipyrine ranged between 75-210 ng/L and 10,11-dihydro-10,11-dihydroxy carbamazepine from 16 to 40 ng/L [53]. Concentrations of PhACs in the river sediments were much lower than the ones found in surface water samples in all reported studies.