Transformation products of pharmaceuticals in the environment: Their fate, (eco)toxicity and bioaccumulation potential.

Nowadays, a huge scientific attention is being paid to the chemicals of emerging concern, which may pose a significant risk to the human and whole ecosystems. Among them, residues of pharmaceuticals are a widely investigated group of chemicals. In recent years it has been repeatedly demonstrated that pharmaceuticals are present in the environment and that some of them can be toxic to organisms as well as accumulate in their tissues. However, even though the knowledge of the presence, fate and possible threats posed by the parent forms of pharmaceuticals is quite extensive, their transformation products (TPs) have been disregarded for long time. Since last few years, this aspect has gained more scientific attention and recently published papers proved their common presence in the environment. Also the interest in terms of their toxicity, bioconcentration and stability in the environment has increased. Therefore, the aim of our paper was to revise and assess the current state of knowledge on the fate and effects resulting from the presence of the pharmaceuticals' transformation drugs in the environment. This review discusses the metabolites of compounds belonging to six major pharmaceutical groups: SSRIs, anticancer drugs, antibiotics, antihistamines, NSAIDs and opioids, additionally discussing other individual compounds for which literature data exist. The data presented in this paper prove that some TPs may be as harmful as their native forms, however for many groups of drugs this data is still insufficient to assess the risk posed by their presence in the environment.

Hydrolytic stability of anticancer drugs and one metabolite in the aquatic environment.

Due to the genotoxic, carcinogenic and teratogenic mechanism of action, anticancer drugs are highly hazardous compounds. Their occurrence, fate, and effects in the environment have not been systematically studied as compared to other medicaments. Therefore, reliable data, including their stability and persistency, is required in order to assess it. Taking into account, that hydrolysis is one of the most important factors regarding stability of chemicals in water, the aim of our study was to investigate the hydrolytic stability of five commonly used anticancer drugs (ifosfamide, cyclophosphamide, 5-fluorouracil, imatinib, and methotrexate) and one metabolite (7-hydroxymethotrexate), as the systematized and coherent data available is limited. The hydrolysis studies have been prepared according to the OECD 111 procedure to obtain standardized and comparable results. The preliminary tests at pH 4, 7, and 9 and 50 °C show that only cyclophosphamide and ifosfamide are unstable, whereas the estimated t1/2 at 25 °C is >1 year for other investigated compounds. Moreover, much more detailed experiments were performed and indicate that at environmentally relevant temperatures, cyclophosphamide, and ifosfamide would be quite persistent in the terms of hydrolytic stability. Moreover, the preliminary investigation on the hydrolysis products was performed.

Hydrolytic stability of selected pharmaceuticals and their transformation products.

The fact that pharmaceuticals are present in the environment has been proven in numerous publications. Nevertheless, their transformation products (mainly metabolites) are detected significantly less often, mainly because they are not included in the detecting methods, even though many of them are excreted from organisms at high rates and may be biologically active or have other properties that make them a potential threat to the environment. One of the most common processes that occur in the aqueous environment is hydrolysis, which may be one of the most important factors influencing the persistency of pharmaceuticals. Therefore four pharmaceuticals (carbamazepine, ibuprofen, tramadol and naproxen) as well as ten metabolites (10,11-dihydro-10-hydroxy carbamazepine, 10,11-dihydro-2-hydroxy carbamazepine, carbamazepine epoxide, 2-hydroxy ibuprofen, ibuprofen carboxylic acid, O-desmethyltramadol, hydroxy metronidazole, N-acetylsulfamethoxazole, 4'-hydroxy diclofenac, and O-desmethylnaproxen) were selected for the hydrolytic stability tests in accordance to OECD 111 Guideline. The preliminary test showed that only carbamazepine epoxide at pH 4, hydroxy metronidazole at pH 9 and 4'-hydroxy diclofenac at pH 4 and 9 were unstable and were included in the extended tests, which resulted in calculation of rate constants and half-lives at the temperature of 20, 50 and 70 °C as well as the activation energy at the pH values in which these compounds were unstable. The obtained results show that carbamazepine epoxide is quite unstable and the half-life at 20 °C was a little more than 8 days. Nevertheless, hydroxy-metronidazole and 4'-hydroxy diclofenac did not degrade at 20 °C for 30 days.

Preliminary evaluation of the application of carbon nanotubes as potential adsorbents for the elimination of selected anticancer drugs from water matrices.

The presence of anticancer drugs in the environment raises a major concern due to their potentially negative impact on living organisms, as they cause, inter alia, teratogenic, mutagenic, carcinogenic effects on growing cells. The main source of these pharmaceuticals in the environment is the ineffectively treated wastewaters, hence the efficient methods for their removal are required. In this study, we have evaluated for the first time the applicability of different Multi-Walled Carbon Nanotubes (MWCNTs) as alternative adsorbents for the removal of three popular anticancer drugs from water matrices, which are detected in waste/hospital waters at the concentrations even up to µg L-1: cyclophosphamide (CP), ifosfamide (IF) and 5-fluorouracil (5-FU). It was observed that adsorption equilibrium time was reached after 20 min for each compound and CNTs. Moreover, CP has the highest sorption potential (Kd up to 1597 L kg-1) for all CNTs and CNTs with the highest surface area have the greatest adsorption capacity. Isotherms were fitted best to the Freundlich model. Significant influence of pH in the range 4-9 and ionic strength was not observed what may indicate that adsorption is not dependent on fluctuation of basic environmental conditions.

Evaluation of the sorption mechanism of ionic liquids onto multi-walled carbon nanotubes.

The knowledge of the sorption mechanism of different chemicals onto third generation carbon sorbents such as carbon nanotubes (CNTs) is needed in order to project systems for the effective removal of pollutants from the environment. This paper reports evaluation of the sorption mechanism of selected ionic liquids (ILs), being considered as potential pollutant in environment, onto various CNTs. CNTs characterized by the smallest diameter and the biggest surface area showed the highest sorption capacity to isolate ILs from an aqueous solution. CNTs with a bigger diameter, a functionalized surface and particularly a helical shape showed a lower sorption capacity. The sorption mechanism has been defined as complex, including van der Waals, π-π and electrostatic interactions with dominating π-π interactions. Due to the relatively high sorption coefficient (355.98 ± 20.69-6397.10 ± 355.42 L kg-1 depending on the IL) the study showed that multi-walled carbon nanotubes can potentially be used to effectively isolate ILs from an aqueous solution. Moreover, proved in this study, the fast sorption kinetic, and uncomplicated regeneration process, leading to an even higher sorption capacity, means that CNTs are promising material which could find potential applications in the treatment of water contaminated by ILs.