title: Toxicity of the mixture of selected antineoplastic drugs against aquatic primary producers.
abstract: 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 EC10-EC50 higher than the predicted, whereas at higher effect concentration (EC90), 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.
authors.affiliation: Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna pot 111, 1000, Ljubljana, Slovenia. tina.elersek@nib.si.
authors.forename: Tina
authors.initials: T
authors.lastname: Elersek
authors.affiliation: Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna pot 111, 1000, Ljubljana, Slovenia.
authors.forename: Sara
authors.initials: S
authors.lastname: Milavec
authors.affiliation: Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna pot 111, 1000, Ljubljana, Slovenia.
authors.forename: Maša
authors.initials: M
authors.lastname: Korošec
authors.affiliation: Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna pot 111, 1000, Ljubljana, Slovenia.|Ecological Engineering Institute, Ljubljanska ulica 9, 2000, Maribor, Slovenia.
authors.forename: Polona
authors.initials: P
authors.lastname: Brezovsek
authors.affiliation: Water and Soil Quality Research Group, Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research, Jordi Girona 18-26, 08034, Barcelona, Spain.
authors.forename: Noelia
authors.initials: N
authors.lastname: Negreira
authors.affiliation: Water and Soil Quality Research Group, Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research, Jordi Girona 18-26, 08034, Barcelona, Spain.
authors.forename: Bozo
authors.initials: B
authors.lastname: Zonja
authors.affiliation: Water and Soil Quality Research Group, Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research, Jordi Girona 18-26, 08034, Barcelona, Spain.
authors.forename: Miren López
authors.initials: ML
authors.lastname: de Alda
authors.affiliation: Water and Soil Quality Research Group, Department of Environmental Chemistry, Institute of Environmental Assessment and Water Research, Jordi Girona 18-26, 08034, Barcelona, Spain.
authors.forename: Damià
authors.initials: D
authors.lastname: Barceló
authors.affiliation: Jožef Stefan Institute, Jamova 39, 1000, Ljubljana, Slovenia.
authors.forename: Ester
authors.initials: E
authors.lastname: Heath
authors.affiliation: Jožef Stefan Institute, Jamova 39, 1000, Ljubljana, Slovenia.
authors.forename: Janez
authors.initials: J
authors.lastname: Ščančar
authors.affiliation: Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, Večna pot 111, 1000, Ljubljana, Slovenia.
authors.forename: Metka
authors.initials: M
authors.lastname: Filipič
mesh_terms: D000970:Antineoplastic Agents / Q000633:toxicity*; D000460:Chlorophyta / Q000187:drug effects*; D005047:Etoposide / Q000633:toxicity; D005472:Fluorouracil / Q000633:toxicity; D000068877:Imatinib Mesylate / Q000633:toxicity; D010839:Phytoplankton / Q000187:drug effects; D046940:Synechococcus / Q000187:drug effects*; D014874:Water Pollutants, Chemical / Q000633:toxicity*
chemical_list: D000970:Antineoplastic Agents; D014874:Water Pollutants, Chemical; D005047:Etoposide; D000068877:Imatinib Mesylate; D005472:Fluorouracil
keywords: 5-fluorouracil; Algae; Antineoplastics; Cisplatin; Cyanobacteria; Etoposide; Imatinib mesylate; Mixture toxicity