process of water chlorination. Toxicity to V. fischeri is similar to the toxicity of parent form.
There were no losses in the water treatment processes in terms of the content of CBZ metabolites. In some cases, the amount of 2-OH-CBZ and Di-OH-CBZ increased after the purification process, which was most likely due to the fact that some CBZ and its metabolites are also excreted in the form of glucuronides.
Not active, concentrations at the level of 4000 ng L−1, concentrations higher than for the native form. It is also a transformation product of CBZ in the process of water chlorination. More toxic to V. fischeri than the native substance.
2-hydroxycarbamazepine(2-OH-CBZ)
More toxic to V. fischeri than the native substance; detected in the environmental samples.
3-hydroxycarbamazepine(3-OH-CBZ)
More toxic to V. fischeri than the native substance; detected in the environmental samples.
10-hydroxycarbamazepine(10-OH-CBZ)
Often detected in environmental samples, more often than other metabolites, although the percentage of this metabolite is low, probably it is a TP of CBZ in WWTP purification processes.
Metopropol (MTP)
β-blocker
<10%
metoprolol acid(MTPA), 60–65%
Detected in the environmental samples at concentrations 10 times higher than for the native form; this substance is also a product of the transformation of other beta-blockers, including atenolol, in the biodegradation process, hence its concentration is almost 10 times higher in effluents than in influents; acute toxicity to V. fischeri has not been demonstrated.
α-hydroxymetoprolol (α-HMTP)
Detected, but only in wastewater, which is suspected to be due to the biodegradability of MTP in the water treatment process; acute toxicity to V. fischeri has not been demonstrated.
O-desmethylmetoprolol (O-DMTP)
MTP biodegradation product; however, it is rapidly biodegradable and therefore not detected in environmental samples.
Sulfamethoxazole (SMX)
Antibiotic
20%
N4-acetylo-sulfamethoxazole (N4-Ac-SMX), 50–70%
Main metabolite of SMX. Excreted in 50–70%. Detected in the environmental samples.
Ciprofloxacin (CIP)
40–50%
CIP is the metabolite of enrofloxacin; metabolites of CIP are less active than CIP itself, moreover they are excreted in smaller amount that native form.
Metronidazol (METR)
20%
hydroxymetronidazol (METR-OH), main metabolite
Active; in treated waters discharged from hospital treatment plants at a concentration of 11 µg L−1; although the concentrations in WWTP wastewater are lower (160 ng L−1).
Ibuprofen (IBU)
NSAIDs
10–15%
2-hydroxy-ibuprofen(2-OH-IBU), 26%
Concentration in influents 6840 ng L−1 while in the effluents 1130 ng L−1; hydroxyl derivatives more toxic to V. fischeri than the native form.
It was found that these compounds are also produced as TPs in the biodegradation process of IBU. CX-IBU is removed by biodegradation, but OH-IBU is stable, therefore it is the dominant TP in purified waters, although there are studies where it has been found that both can be biodegradable – it depends on the test conditions.
carboxy-ibuprofen(CX-IBU), 43%
Concentration in influents 38.4 μg L−1 while in the effluents 10.6 μg L−1.
1-hydroxy-ibuprofen(1-OH-IBU)
The percentage of this metabolite is lower than for others; this is reflected in its concentrations detected in wastewaters, lower than for 2-OH-IBU; however, hydroxyl derivatives are more toxic than the native form to V. fischeri.
Diclofenac (DIC)
5–10%
4-hydroxydiclofenac(4-OH-DCF), main metabolite, 16%
Concentration in WWTP effluents at the level of 1600 ng L−1.
5-hydroxydiclofenac(5-OH-DCF), 6,1%
Concentration in WWTP effluents at the level of 860 ng L−1.
4-hydroxydiclofenac dehydrate (4-OH-DCF-H2O)
Concentration in WWTP effluents at the level of 660 ng L−1.
Ketoprofen (KET)
20%
glucuronide-KET 80%
Excreted mainly in the form of glucuronides, which are unstable, which leads to the formation of the native form.
Naproxen (NPX)
<1%
6-O-desmethyl-naproxen (6-O-DMNPX) (<1%)
It is a metabolites, but it is also produced during the biodegradation process in WWTP.
NPX and 6-O-DMNPX excreted mainly as coniugates (66–92%)
Tramadol (TRA)
Opioid painkiller
30%
O-desmethyl-tramadol (O-DMTRA)
Active metabolite.
Fluoxatine (FLX)
Antidepressant
11%
Norfluoxetine(NOR-FLX)
Venlafaxine (VNF)
5%
O-desmethylvenlafaxine (O-DM-VNF)
Estron (E1)
Steroid hormones
2-hydroxyestrone (2-OH-E1)
Detected at very low concentrations (max. 14 ng L−1).
4-hydroxyestrone (4-OH-E1)
Detected at very low concentrations (max. 14 ngL−1).
Tamoxifen (TAM)
Anticancer drug
<30%
Hydroxytamoxifen (OH-TAM)
Active metabolite.
endoxifen
Active metabolite.
Cyclophosphamide (CF)/ ifosfamide (IF)
carboxyphosphamide
4-OH-cyclophosphamide/ 4-OH-ifosfamide
Active metabolites, but unstable.
Methothrexate (MET)
7-hydroxymethothrexate(7-OH-MET)
Active metabolite and TPs – it is produces during the MET biodegradation; however, it is stable.
Fenbendazole (FEN)
Antiparasites
fenbendazole sulfoxide(FEN-SO)oxfendazol (OXFEN)
Active metabolite.
2.1.4 Legislation
One of the biggest concerns resulting from the presence of pharmaceutical residues in the environment is the lack of sufficient data to evaluate their real risk to human health and other organisms in the ecosystem. This problem is getting even more complicated if the TPs are taken into account, which in many cases have not yet been sufficiently identified or their (eco)toxicity has not been determined. For all the mentioned reasons, the scientific community and regulatory and authority agencies started to pay special attention to the problem of the presence of pharmaceuticals and their TPs in the environment by introducing specific guidelines on their risk assessment and water policy actions (EU Watch List), as well as supporting and founding research projects concerning this problem. Currently, one of the most important regulations is the European Watch List (WL) for emerging water pollutants, which is aimed at increasing monitoring for substances with a significant risk for human health and the environment in order to perform a future EU-wide risk assessment. Several pharmaceuticals have been listed on the WL. However, it must also be stated that such WL is updated, and it includes chemicals that need to be monitored by EU Member States in surface water at least once per year for 4 years. The first Watch List was established by the Commission Implementing Decision (EU) 2015/4951 in 2015 [18], and it included such pharmaceuticals as:
It was updated in 2018 by Commission Implementing Decision (EU) 2018/840 [19]. During this update, the Commission removed diclofenac (due to its strong monitoring background) from the WL; however, two antibiotics (amoxicillin and ciprofloxacin) were added to the list:
The selection of candidate substances was based on hazard properties, the availability of reliable safety thresholds (such as the contribution to antimicrobial resistance) and the availability of proper analytical methods for their monitoring in the environment.
Finally, in 2020 the 3rd WL was adopted by the Commission Implementing Decision (EU) 2020/1161 [20]. In terms of pharmaceuticals, it includes only two
process of water chlorination. Toxicity to V. fischeri is similar to the toxicity of parent form.