Occurrence and Fate of the Cytostatic Drugs Cyclophosphamide and Ifosfamide in Wastewater and Surface Waters

Abstract

The two oxazaphosphorine compounds cyclophosphamide and ifosfamide are important cytostatic drugs used in the chemotherapy of cancer and in the treatment of autoimmune diseases. Their mechanism of action, involving metabolic activation and unspecific alkylation of nucleophilic compounds, accounts for genotoxic effects described in the literature and is reason for environmental concern. The occurrence and fate of cyclophosphamide and ifosfamide were studied in wastewater treatment plants (WWTPs) and surface waters in Switzerland, using a highly sensitive analytical method based on solid-phase extraction and liquid chromatography tandem mass spectrometry. The compounds were detected in untreated and treated wastewater at concentrations of <0.3-11 ng/L, which corresponded well with concentrations predicted from consumption data and typical renal excretion rates. Weekly loads determined in influent and effluent wastewater were comparable and suggested a high persistence in WWTPs. Furthermore, no degradation was observed in activated sludge incubation experiments within 24 h at concentrations of approximately 100 ng/L. Processes that may be relevant for elimination in natural waterbodies were studied with a set of incubation experiments in the laboratory. After extrapolation to natural conditions in surface waters, a slow dark-chemical degradation (half-lives on the order of years) is the most important transformation process. Degradation by photochemically formed HO* radicals may be of some relevance only in shallow, clear, and nitrate-rich waterbodies but could be further exploited for elimination of these compounds by advanced oxidation processes, i.e., in a treatment of hospital wastewater. In surface waters, concentrations ranged from < or =50 to 170 pg/L and were thus several orders of magnitude lower than the levels at which acute ecotoxicological effects have been reported in the literature (mg/L range). However, due to a lack of studies on chronic effects on aquatic organisms and data on occurrence and effects of metabolites, a final risk assessment cannot be made.