**Influence of Selected Antidepressants on the Ciliated Protozoan** *Spirostomum ambiguum***: Toxicity, Bioaccumulation, and Biotransformation Products**

**Grzegorz Nał ˛ecz-Jawecki 1,\*, Milena Wawryniuk 1, Joanna Giebułtowicz 2, Adam Olkowski 1 and Agata Drobniewska 1,\***

1 Department of Environmental Health Sciences, Faculty of Pharmacy, Medical University of Warsaw, ul. Banacha 1, 02-097 Warszawa, Poland; mwawryniuk@wum.edu.pl (M.W.); olek\_adam@interia.pl (A.O.)

 25 March 2020


Academic Editor: Jolanta Kumirska Received:21February2020; Accepted:20March2020;Published:

**Abstract:** The present study aimed to evaluate the e ffect of the most common antidepressants on aquatic protozoa. *Spirostomum ambiguum* was used as the model protozoan. The biological activity of four antidepressants, namely fluoxetine, sertraline, paroxetine, and mianserin, toward *S. ambiguum* was evaluated. Sertraline was found to be the most toxic drug with EC50 values of 0.2 to 0.7 mg/L. The toxicity of the antidepressants depended on the pH of the medium and was the highest in alkaline conditions. Sertraline was also the most bioaccumulating compound tested, followed by mianserin. Slow depuration was observed after transferring the protozoa from the drug solutions to a fresh medium, which indicated possible lysosomotropism of the tested antidepressants in the protozoa. The biotransformation products were identified using a high-resolution mass spectrometer after two days of incubation of the protozoa with the tested antidepressants. Four to six potential biotransformation products were observed in the aqueous phase, while no metabolites were detected in the protozoan cells. Because of the low abundance of metabolites in the medium, their structure was not determined.

**Keywords:** Spirotox; fluoxetine; sertraline; paroxetine; mianserin; pharmaceuticals in the environment
