Toxicity of the mixture of selected antineoplastic drugs against aquatic primary producers

• Published in: Environmental science and pollution research international Vol. 23; no. 15; pp. 14780 - 14790
• Main Authors: Elersek, Tina, Milavec, Sara, Korošec, Maša, Brezovsek, Polona, Negreira, Noelia, Zonja, Bozo, de Alda, Miren López, Barceló, Damià, Heath, Ester, Ščančar, Janez, Filipič, Metka
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.08.2016; Springer Nature B.V
• Subjects: 5-Fluorouracil; Algae; Antineoplastic Agents - toxicity; Antineoplastic drugs; Aquatic environment; Aquatic plants; Aquatic Pollution; Atmospheric Protection/Air Quality Control/Air Pollution; Cancer therapies; Chlorophyta - drug effects; Cisplatin; Cyanobacteria; Drug development; Drugs; Earth and Environmental Science; Ecotoxicology; Environment; Environmental Chemistry; Environmental Health; Etoposide; Etoposide - toxicity; Experiments; Fate and Effects of the Residues of Anticancer Drugs in the Environment; Fluorouracil - toxicity; Imatinib; Imatinib Mesylate - toxicity; Kinases; Personal grooming; Pharmaceutical industry; Phytoplankton; Phytoplankton - drug effects; Plankton; Pollutants; Pseudokirchneriella subcapitata; Retention time; Synechococcus - drug effects; Synechococcus leopoliensis; Synergistic effect; Toxicity; Waste Water Technology; Water Management; Water Pollutants, Chemical - toxicity; Water Pollution Control; Water treatment; Germany; Slovenia; 5-fluorouracil; Algae; Antineoplastics; Imatinib mesylate; Cyanobacteria; Etoposide; Mixture toxicity; Cisplatin
• ISSN: 0944-1344; 1614-7499
• DOI: 10.1007/s11356-015-6005-2

The residues of antineoplastic drugs are considered as new and emerging pollutants in aquatic environments. Recent experiments showed relatively high toxicity of 5-fluorouracil (5-FU), imatinib mesylate (IM), etoposide (ET) and cisplatin (CP) that are currently among most widely used antineoplastic drugs, against phytoplankton species. In this study, we investigated the toxic potential of the mixture of 5-FU + IM + ET against green alga Pseudokirchneriella subcapitata and cyanobacterium Synechococcus leopoliensis, and the stability and sorption of these drugs to algal cells. Toxic potential of the mixture was predicted by the concepts of ‘concentration addition’ and ‘independent action’ and compared to the experimentally determined toxicity. In both test species, the measured toxicity of the mixture was at effects concentrations EC 10 –EC 50 higher than the predicted, whereas at higher effect concentration (EC 90 ), it was lower. In general, P. subcapitata was more sensitive than S. leopoliensis . The stability studies of the tested drugs during the experiment showed that 5-FU, IM and CP are relatively stable, whereas in the cultures exposed to ET, two transformation products with the same mass as ET but different retention time were detected. The measurements of the cell-linked concentrations of the tested compounds after 72 h exposure indicated that except for CP (1.9 % of the initial concentration), these drugs are not adsorbed or absorbed by algal cells. The results of this study showed that in alga and cyanobacteria exposure to the mixture of 5-FU + ET + IM, in particular at low effect concentration range, caused additive or synergistic effect on growth inhibition, and they suggest that single compound toxicity data are not sufficient for the proper toxicity prediction for aquatic primary producers.