Biodegradability of the anti-tumour agents 5-fluorouracil, cytarabine, and gemcitabine:: Impact of the chemical structure and synergistic toxicity with hospital effluent

Most anti-tumour agents are known to be carcinogenic, mutagenic, teratogenic, embryotoxic or fetotoxic. Only little is known about the environmental impact of pharmaceuticals. Unmetabolized active substances are excreted and will show up in municipal wastewater. Therefore, we examined the biodegradability of the widely used antitumour agent 5-fluorouracil (5-FU), also as an example for assessing the impact of hospital effluent on the biodegradation of a test compound. The biodegradability of the structurally similar anti-tumour agents cytarabine and gemcitabine was also examined. Test systems used were the closed bottle test (OECD 301 D) and the modified Zahn-Wellens test (OECD 302 B). 5-FU was not biodegradable in the closed bottle test (CBT) nor in the Zahn-Wellens test (ZWT). At the highest concentration of 5-FU, with hospital effluent an inhibition of the degradation of substances present in hospital effluent was observed, probably as a result of a synergistic effect by 5-FU with antibiotics present in hospital sewage. Gemcitabine was biodegraded 42% in the CBT. The prolongation of the test period to 40 days only improved the result to 45%. In the ZWT, the biodegradation of gemcitabine was 50%. Cytarabine was partially biodegraded in the CBT (50%), but only after an adaptation period of 20 days. After a test prolongation to 40 days, the degree of biodegradation was 80%. In the ZWT, the biodegradability was > 95% after only a few days.