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 nontarget organisms. 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 mu g/L, with stronger effects occurring at measured concentrations of 178 mu g/L and above. At 77 mu g/L and above, a significant increase in adult body length and offspring production/brood was found, although the time between brood releases remained unaffected. The pre-adult surviving fraction was significantly reduced (by 44%) at 765 mu g/L. For a mechanistic evaluation of these observations, we used a bioenergetics model for N. spinipes based on the dynamic energy budget theory. Toxicokinetic and toxicodynamic submodels were used to dynamically simulate the chemical uptake and elimination, as well as dose-response relationships for hypothetical physiological modes of action and survival over time. Although none of the commonly invoked physiological modes of action, acting on assimilation, maintenance, growth, or offspring production, could explain the observed combination of effects, a newly proposed physiological mode of action 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 physiological mode of action 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 SSRIs at higher ecological levels. Environ Toxicol Chem 2021;00:1-12. (c) 2021 SETAC