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Assessing the environmental hazard of individual and combined pharmaceuticals: acute and chronic toxicity of fluoxetine and propranolol in the crustacean Daphnia magna

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Abstract

Pharmaceuticals are widespread emerging contaminants and, like all pollutants, are present in combination with others in the ecosystems. The aim of the present work was to evaluate the toxic response of the crustacean Daphnia magna exposed to individual and combined pharmaceuticals. Fluoxetine, a selective serotonin re-uptake inhibitor widely prescribed as antidepressant, and propranolol, a non-selective β-adrenergic receptor-blocking agent used to treat hypertension, were tested. Several experimental trials of an acute immobilization test and a chronic reproduction test were performed. Single chemicals were first tested separately. Toxicity of binary mixtures was then assessed using a fixed ratio experimental design. Five concentrations and 5 percentages of each substance in the mixture (0, 25, 50, 75, and 100%) were tested. The MIXTOX model was applied to analyze the experimental results. This tool is a stepwise statistical procedure that evaluates if and how observed data deviate from a reference model, either concentration addition (CA) or independent action (IA), and provides significance testing for synergism, antagonism, or more complex interactions. Acute EC50 values ranged from 6.4 to 7.8 mg/L for propranolol and from 6.4 to 9.1 mg/L for fluoxetine. Chronic EC50 values ranged from 0.59 to 1.00 mg/L for propranolol and from 0.23 to 0.24 mg/L for fluoxetine. Results showed a significant antagonism between chemicals in both the acute and the chronic mixture tests when CA was adopted as the reference model, while absence of interactive effects when IA was used.

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Acknowledgements

We are grateful to Valentina Stignani for her assistance in the laboratory.

Funding

The Italian Ministry of Education, University and Research provided financial support for the conduct of the research and granted a Ph.D. fellowship to the first author, who carried out the study in partial fulfillment of the requirements for the doctorate in Environmental Sciences.

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  1. Department of Biological, Geological and Environmental Sciences (BiGeA), University of Bologna, via Sant’Alberto 163,, Ravenna, 48123, Italy

    Valentina Varano, Elena Fabbri & Andrea Pasteris

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  1. Valentina Varano
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  2. Elena Fabbri
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Correspondence to Andrea Pasteris.

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This study did not involve any research conducted on human participants. No specific permissions were necessary, because the existing legislation on the welfare of experimental animals is not applicable and the study did not involve the collection of endangered or protected species.

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Varano, V., Fabbri, E. & Pasteris, A. Assessing the environmental hazard of individual and combined pharmaceuticals: acute and chronic toxicity of fluoxetine and propranolol in the crustacean Daphnia magna . Ecotoxicology 26, 711–728 (2017). https://doi.org/10.1007/s10646-017-1803-6

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