title: Antineoplastic compounds in the environment-substances of special concern.
abstract: Antineoplastic drugs are important in the treatment of cancer. Some interact directly with the deoxyribonucleic acid (DNA) and are of utmost importance in terms of risk. As highly active compounds, antineoplastics and their metabolites are largely excreted into wastewater and are found in the aquatic environment up to the lower μg/L range. Their predicted environmental concentrations are often below the action limit set in the European Medicines Agency (EMA) guideline. An in-depth risk assessment regarding their presence and effects in the aquatic environment is often not performed, and there is a lack of knowledge. This study considered whether there is an underestimation of possible risks associated with the presence of antineoplastic drugs with regard to trigger value stated in the EMA and FDA guidelines. In a balance, we identified a total of 102 active pharmaceutical ingredients of the ATC-group L01 (antineoplastic agents), which are environmentally relevant. In Germany, 20.7 t of antineoplastic agents was consumed in 2012. The share of drugs with DNA-damaging properties increased within the last 6 years from 24 up to 67 %. Solely, capecitabine and 5-fluorouracil amount together 8 t-which corresponds to 39 % of the total antineoplastic consumption. Around 80 % of the total mass consumed could be attributed to prescriptions issued by office-based practitioners and is mostly excreted at home. Based on the different mode of actions, a case-by-case evaluation of the risk connected to their presence in the environment is recommended. DNA-damaging drugs should be assessed independently as no action limit can be assumed.
authors.affiliation: Institute of Sustainable and Environmental Chemistry, Leuphana University Lüneburg, Scharnhorststraße1, 21335, Lüneburg, Germany. klaus.kuemmerer@leuphana.de.
authors.forename: Klaus
authors.initials: K
authors.lastname: Kümmerer
authors.affiliation: Institute of Sustainable and Environmental Chemistry, Leuphana University Lüneburg, Scharnhorststraße1, 21335, Lüneburg, Germany.
authors.forename: Annette
authors.initials: A
authors.lastname: Haiß
authors.affiliation: Department of Environmental Health Sciences, University Medical Centre Freiburg, Breisacher Str. 115B, 79106, Freiburg, Germany.
authors.forename: Armin
authors.initials: A
authors.lastname: Schuster
authors.affiliation: Federal Environment Agency, Pharmaceuticals, Washing and Cleansing Agents, Wörlitzer Platz 1, 06844, Dessau, Germany.
authors.forename: Arne
authors.initials: A
authors.lastname: Hein
authors.affiliation: Federal Environment Agency, Pharmaceuticals, Washing and Cleansing Agents, Wörlitzer Platz 1, 06844, Dessau, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Ebert
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D004249:DNA Damage; D004781:Environmental Exposure; D004784:Environmental Monitoring; D004785:Environmental Pollutants / Q000633:toxicity*; D005858:Germany; D006801:Humans; D018570:Risk Assessment
chemical_list: D000970:Antineoplastic Agents; D004785:Environmental Pollutants
keywords: Action limit; Antineoplastic agents; Aquatic environment; Cytotoxic; DNA interaction; EMA; Risk assessment