Environmental fate and effects of pharmaceuticals in the aquatic environment

Abstract

Pharmaceuticals in the environment have for several decades been recognized as emerging contaminants. After use, most pharmaceutical ingredients are excreted both as active compounds and inactive metabolites and transferred as a part of the household wastewater, through the sewage systems where it is received by wastewater treatment plants. However, wastewater treatment plants are not designed to handle these pharmaceutical components causing them to ultimately end up in the aquatic environment, occasionally even at higher concentrations in the wastewater effluent compared to the influent. As a result, pharmaceuticals have been quantified in all matrixes of the aquatic environment where they exist as mixtures. Historically, research has primarily centered around pharmaceutical presence in the water, yet some pharmaceuticals are prone to partition to the sediment. As such, pharmaceutical exposure to benthic invertebrates and their influence on the fate of pharmaceuticals are generally uninvestigated. Furthermore, as pharmaceuticals are designed to yield a therapeutic effect at low internal concentrations, their presence in the aquatic environment might cause both lethal and sublethal effects in wildlife. The objective of this PhD project was to investigate the environmental fate and ecological effects of pharmaceuticals in the aquatic environment and the complexity of including sediment in the ecotoxicological matrix. To achieve this, I focused on six commonly detected pharmaceuticals—citalopram, escitalopram, cetirizine, diclofenac, carbamazepine, and metoprolol—selected based on their frequent environmental occurrence and their diverse physical-chemical properties and modes of action. Specifically, these compounds represent different therapeutic classes and biological targets, including selective serotonin reuptake inhibition (citalopram, escitalopram), histamine H1 receptor antagonism (cetirizine), cyclooxygenase inhibition (diclofenac), voltage gated sodium channel blocking (carbamazepine), and β1 adrenergic receptor antagonism (metoprolol). Their contrasting modes of action provided a useful framework for exploring how pharmaceuticals with different biological functions and target affinities interact with aquatic organisms. Secondly, the organisms Coenagrion hastulatum, Aeshna juncea, Corophium volutator, Hydrobia ventrosa, Capitella teleta, and Salmo trutta were chosen with a focus on high ecological importance and common abundance in the aquatic environment. Together with co-authors, I assessed how pharmaceuticals with varying chemical-physical properties and function partition between environmental matrixes, their lethal and sublethal effects on organisms, and how dietary exposure in fish can result in different tissue distributions. We found that cetirizine and citalopram, individually and in a mixture, caused adverse behavioral effects in the predator-prey interactions between the two odonate nymphs after short-term exposure. Where cetirizine exposure made A. juncea less successful when faced with a single prey, citalopram exposure made A. juncea less efficient predators when faced with multiple pray, and A. juncea exposed to both cetirizine and the mixture were more successful predators when they started hunting when faced with multiple prey. We established that lethal concentrations of diclofenac and citalopram to C. volutator are beyond environmentally realistic concentrations and that their environmental distribution (e.g., changes in sediment concentration over time) should be counted for when assessing the effects which can be done effectively by modelling. Furthermore, the mixture toxicity of diclofenac and citalopram was accurately described by the concept of concentration addition but synergistic relative to independent action. We also found that pharmaceuticals partition differently between water and sediment depending on physical-chemical properties (e.g., hydrophobicity and ionizability) and that the presence of H. ventrosa and C. teleta generally lowered the overall concentrations of escitalopram, carbamazepine, and metoprolol. However, C. teleta appeared to increase the sediment concentration of escitalopram to concentrations exceeding the measured start concentrations, suggesting that C. teleta could be facilitating de-conjugation of escitalopram. Finally, our results indicate that the different physical-chemical properties and mode of action of escitalopram, carbamazepine, and metoprolol affect tissue distribution in S. trutta after dietary exposure. These findings call for more knowledge and a better understanding of how pharmaceuticals can affect interactions between organisms but also how organisms interacting with different substrates can affect the fate of the pharmaceuticals both as individual contaminants and in multi-compound mixtures.