In vitro tests aiding ecological risk assessment of ciprofloxacin, tamoxifen and cyclophosphamide in range of concentrations released in hospital wastewater and surface water

Ciprofloxacin (CIP), tamoxifen (TAM) and cyclophosphamide (CP) which are often used in anticancer treatment are released in hospital effluent and into the environment. Although the concentrations are low (from ng/L to μg/L), no data exist concerning their ecotoxicological impact. In this study two biomarkers of early effect were performed on hepatic cells (HepG2): cell viability and genotoxicity (DNA breaks) using cell proliferative assay and comet assay, respectively. These data were compared with two standardized ecotoxicological tests: algaltoxkit F™ and microtox®. Cells were exposed to an increasing amount of an individual drug or in a mixture for 24, 48 or 72 h. The time-exposure of bacteria and algae ranged between 5 and 30 min and 72 h, respectively. A non-monotonic dose–response on cell viability was observed when HepG2 cells were exposed to TAM alone or in the presence of CIP. The same scheme was observed with microtox® when the bacteria were exposed to the mixtures. On the other side, an individual drug does not induce any DNA breaks on hepatic cells, whereas a mixture leads to a dose dependent increase of DNA breaks. Similarly a positive response was observed with algaltoxkit F™ only with mixtures. Synergistic effects observed when drugs are in a mixture highlight the importance of investigating the ecotoxicological effects of contaminants at low concentrations and in mixtures. Keywords: Ciprofloxacin, Tamoxifen, Cyclophosphamide, Wastewater, Hormesis, Bioassays