Benzalkonium Chloride and Anticancer Drugs in Binary Mixtures: Reproductive Toxicity and Genotoxicity in the Freshwater Crustacean Ceriodaphnia dubia.

Benzalkonium chloride (BAC) is a cationic surfactant commonly used as a disinfectant. Its ubiquitous nature is the result of high usage and frequent discharge into the environment and evidence of interaction with numerous contaminants, such as pharmaceutical active compound residues. Anticancer drugs, among these compounds, are able to exert eco-genotoxic effects at sub ng-µg/L. The purpose of this study was to assess the reproductive toxicity and the genotoxicity of 5-fluorouracil (5-FU), cisplatin (CDDP), etoposide (ET), and imatinib mesylate (IM)-binary mixtures combined with BAC in Ceriodaphnia dubia. The effects of the mixtures were assessed under the assumption of independent action in experiments that applied two effect levels. The type of interaction was not the same over the range of effect sizes. The combined action experiment on reproduction showed an antagonistic effect at higher effect levels for all binary combinations, except for BAC/IM, whereas independent action was observed in all mixtures at a low effect level. The results of binary combinations on genotoxicity showed antagonistic effects for BAC + ET and BAC + CDDP, whereas independence was expressed in BAC + IM and BAC + 5-FU. The antagonistic interactions still led to higher effects than those observed after single exposures at the same doses in most cases. The effects of mixtures of drugs should be taken into account for environmental risk assessment.