Insight into the Sorption of 5-Fluorouracil and Methotrexate onto Soil–pH, Ionic Strength, and Co-Contaminant Influence

Abstract

Nowadays anticancer drugs (ADs), like other pharmaceuticals, are recognized as new emerging pollutants, meaning that they are not commonly monitored in the environment; however, they have great potential to enter the environment and cause adverse effects there. The current scientific literature highlights the problem of their presence in the aquatic environment by publishing more and more results on their analytics and ecotoxicological evaluation. In order to properly assess the risk associated with the presence of ADs in the environment, it is also necessary to investigate the processes that are important in understanding the environmental fate of these compounds. However, the state of knowledge on mobility of ADs in the environment is still very limited. Therefore, the main aim of our study was to investigate the sorption potential of two anticancer drugs, 5-fluorouracil (5-FU) and methotrexate (MTX), onto different soils. Special attention was paid to the determination of the influence of pH and ionic strength as well as presence of co-contaminants (cadmium (Cd2+) and another pharmaceutical—metoprolol (MET)) on the sorption of 5-FU and MTX onto soil. The obtained distribution coefficient values (Kd) ranged from 2.52 to 6.36 L·kg−1 and from 6.79 to 12.94 L·kg−1 for 5-FU and MTX, respectively. Investigated compounds may be classified as slightly or low mobile in the soil matrix (depending on soil). 5-FU may be recognized as more mobile in comparison to MET. It was proved that presence of other soil contaminants may strongly influence their mobility in soil structures. The investigated co-contaminant (MET) caused around 25-fold increased sorption of 5-FU, whereas diminished sorption of MTX. Moreover, the influence of environmental conditions such as pH and ionic strength on their sorption has been clearly demonstrated.

Assessing the risks of capecitabine and its active metabolite 5-fluorouracil to freshwater biota

“…Besides these methodological constrains, the toxicity of 5-FU might also be influenced by the ionic strength of the standard medium, which can also explain the large variation in the response to this drug observed in our study (MBL; OECD 2011 ). Previous studies have reported that even slight changes in the pH (for instance of half unit, that may be a result of the addition of algae at the start of the assay and/or during the assay due to the algae own metabolism) may lead to the formation of different species of the same compound (Markiewicz et al 2021 ). In that same study (Markiewicz et al 2021 ), the authors studied the acid–base equilibrium of 5-FU along with another cytostatic drug.…”

“…Previous studies have reported that even slight changes in the pH (for instance of half unit, that may be a result of the addition of algae at the start of the assay and/or during the assay due to the algae own metabolism) may lead to the formation of different species of the same compound (Markiewicz et al 2021 ). In that same study (Markiewicz et al 2021 ), the authors studied the acid–base equilibrium of 5-FU along with another cytostatic drug. They found that at a pH closer to 9, dianionic species of 5-FU started to be formed and become predominant from this pH onwards, whilst at lower pH (closer to 7), 5-FU exists mostly in neutral and monoanionic forms (Markiewicz et al 2021 ).…”

“…In that same study (Markiewicz et al 2021 ), the authors studied the acid–base equilibrium of 5-FU along with another cytostatic drug. They found that at a pH closer to 9, dianionic species of 5-FU started to be formed and become predominant from this pH onwards, whilst at lower pH (closer to 7), 5-FU exists mostly in neutral and monoanionic forms (Markiewicz et al 2021 ). Despite that it has been argued before that dianionic forms of 5-FU are strongly limited in aqueous media (Wielińska et al 2019 ), one cannot say for sure if the presence, even in smaller amounts of these other forms, may be more or less toxic to aquatic biota as no evidence has been provided so far in the literature.…”