Predicting concentrations of the cytostatic drugs cyclophosphamide, carboplatin, 5-fluorouracil, and capecitabine throughout the sewage effluents and surface waters of Europe

The present study evaluated the potential environmental concentrations of 4 cytostatic (also known as cytotoxic) drugs in rivers. The antimetabolite 5-fluorouracil (5FU) and its pro-drug capecitabine were examined based on their very high use rates, cyclophosphamide (CP) for its persistence, and carboplatin for its association with the metal element platinum. The study combined drug consumption information across European countries, excretion, national water use, and sewage removal rates to derive sewage effluent values across the continent. Results showed considerable variation in the popularity of individual cytostatic drugs across Europe, including a 28-fold difference in 5FU use and 15-fold difference in CP use. Such variations could have a major effect on the detection of these compounds in effluent or river water. Overall, capecitabine and CP had higher predicted levels in effluent than 5FU or carboplatin. Predicted effluent values were compared with measurements in the literature, and many non-detects could be explained by insufficient limits of detection. Linking the geographic based water resources model GWAVA with this information allowed water concentrations throughout 1.2 million km of European rivers to be predicted. The 90th percentile (worst case) prediction indicated that, with the exception of capecitabine, more than 99% of Europe's rivers (by length) would have concentrations below 1 ng/L for these cytostatic drugs. For capecitabine, 2.2% of river length could exceed 1 ng/L.