Making Sense of Life-History Effects of the Antidepressant Citalopram in the Copepod Nitocra spinipes Using a Bioenergetics Model.

The global consumption of human antidepressants has steadily increased over the last years. The most-widely prescribed antidepressants are the selective serotonin reuptake inhibitors (SSRIs) which have been linked to various life-history effects in non-target organisms. Here, we investigated the effects of the SSRI citalopram hydrobromide on the life history of the copepod Nitocra spinipes. Slight but significant developmental delay effects were observed at nominal concentrations of 0.1 and 1 µg/L with stronger effects occurring at measured concentrations of 178 µg/L and above. At 77 µg/L and above a significant increase of the adult body length and the offspring production per brood were found, although the time between brood releases remained unaffected. The pre-adult surviving fraction was significantly reduced (by 44 %) at 765 µg/L. For a mechanistic evaluation of these observations, we used a bioenergetics model for N. spinipes based on the Dynamic Energy Budget (DEB) theory. Toxicokinetic and toxicodynamic (TKTD) submodels were used to dynamically simulate the chemical uptake and elimination, as well as dose-response relationships for hypothetical physiological modes of action (pMoAs) and the survival over time. Although none of the commonly invoked pMoAs, acting on assimilation, maintenance, growth, or offspring production, could explain the observed combination of effects, a newly proposed pMoA acting on the process of maturation delivered correct predictions in terms of each effect's direction. The model fits could be further improved by allowing for a gentler concentration-effect slope and by adding an auxiliary pMoA acting on the reproduction efficiency. The quantitative explanations provided in the present study offer a starting point for exploratory simulation studies investigating the effects of SSRI at higher ecological levels. This article is protected by copyright. All rights reserved.