Treatment-driven removal efficiency, product formation, and toxicity evolution of antineoplastic agents: Current status and implications for water safety assessment

Antineoplastic compounds, designed for chemotherapeutic anticancer therapy, have become emerging contaminants of global concern over the past decade due to their ubiquitous occurrence, environmental persistence, and multiple adverse effects on aquatic ecosystems. Increasing efforts have been devoted to developing efficient strategies for remediating water containing these micropollutants. In this study, the physicochemical properties, natural attenuation, and chemical reactivity with aqueous oxidizing species of five antineoplastic drugs with the highest environmental prevalence (i.e., tamoxifen, cyclophosphamide, ifosfamide, 5-fluorouracil, and methotrexate) were summarized. The removal performance, transformation products (TPs) of varying structures, overall reaction pathways, and toxicity evolution during different treatments were evaluated and discussed. Additionally, the biodegradability and multi-endpoint toxicity of each TP were predicted using in silico QSAR software. Depending on their distinct inherent structures, the reactivity of the antineoplastics with oxidizing species varied, with hydroxyl radicals exhibiting unparalleled merits in rapid oxidation. Complete elimination of these contaminants was observed during oxidative treatments, but with inadequate mineralization. Notably, the increase in toxicity within multiple processes was determined based on both experimental bioassays and theoretical predictions. This may be attributed to the adverse effects induced by the large number of identified and unknown TPs individually and in combination. Together with the environmental persistence and low biodegradability of most TPs, these results necessitate the application of efficient post-treatments in conjunction with a more thorough water safety evaluation (e.g., using high-throughput screening) of the mixtures of treated water and wastewater.