plants. In contrast, 528 substances were determined in surface water, groundwater and drinking water all over the world. However, 19 of them have been detected in all five United Nation regions [17]: 17-α-ethynylestradiol, 17-β-estradiol, acetylsalicylic acid, carbamazepine, ciprofloxacin, clofibric acid, diclofenac, estriol, estrone, ibuprofen, indomethacin, ketoprofen, naproxen, paracetamol, sulfamethazine, sulfamethoxazole, triclocarban, triclosan and trimethoprim.
In comparison with the previous version of these data five substances (indomethacin, ketoprofen, sulfamethazine, triclocarban and triclosan) have now been detected in all five UN regions [17]. Even though there have been more than 50 different matrices analysed, it has been proved that pharmaceutical residues were mostly found in groundwater, surface water and drinking water, as well as soil and sediments [17]. Moreover, it was also observed that the most commonly detected pharmaceuticals in surface water or wastewater worldwide belong to the group of antibiotics and analgesic/anti-inflammatories [1]. Usually, more than 40% of the analysed samples were positive for at least one target, with concentrations for half of them <0.1 μg L−1 [1]. Furthermore, most of the published data on the Maximal Environmental Concentrations (MECs) come from China, USA, Spain and Germany [17].
In general, their concentrations are in the range of ng L−1 up to μg L−1 in the water bodies (wastewater, surface water, ground water and drinking water) and from μg kg−1 up to mg kg−1 in sludge/soils or sediments. In Figure 2.2 the range of pharmaceutical concentrations in different environmental samples has been presented based on the previously reviewed data in [1] and [17].
Figure 2.2 Pharmaceuticals occurrence in the environment. Average range of concentration based on the data presented in *[1], examples of MECs based on the data in **[17] (applied abbreviations: E2 – estradiol, EE2 – 17--estradiol, DIC – diclofenac, AZ – azithromycin, CL – clarithromycin, ER – erythromycin, CIP – ciprofloxacin, AMX – amoxicillin, IBU – ibuprofen, TMP – trimethoprim).
Table 2.1 Pharmaceuticals and their selected transformation products [12-14].
| Pharmaceutical (native form) | Therapeutic group | Excretion of parent form [%] | Main metabolites/ Transformation products | Justification | Additional comments |
| Carbamazepine (CBZ) | Antidepressant/antiepileptic | 5% | carbamazepine-10,11-epoxide(CBZ-Ep) | Active metabolite; however, unstable; can be transformed to Di-OH-CBZ, hence the concentration in the environment is usually lower than for Di-OH-CBZ; detected in the environment up to 4000 ng L−1. It is also a transformation product of CBZ in the 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. |
| 10,11-dihydro-trans-10,11-dihydroxy-carbamazepine(Di-OH-CBZ) | 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
|