Interaction and Fate of Pharmaceuticals in Soil-Crop Systems

The topic of this book is dedicated to the analysis, fate, metabolism, effects, and remediation of pharmaceutically active compounds in water-soil-biota systems. While the majority of readers are likely to already have a broad understanding of potential entry points, flows, transformation pathways, and temporary and permanent sinks of drugs in the environment, the objectives of this first chapter are fourfold: (a) to provide a concise overview of the journey a drug takes from its inception at the laboratory bench to the desk of the reviewer at the regulatory agency; (b) to understand the biological and physiological processes a drug undergoes from administration to humans – or to the animal in case of veterinary medicines – to their excretion and ultimately discharge into wastes; (c) to describe the physico-chemical space small-molecule drugs reside in as this characteristic largely governs their later environmental fate; (d) to review their presence, fate, and metabolism in crops and plants determined using innovative analytical methods; as well as (e) to evaluate the effects and remediation of drugs in crops and biota.

This chapter focuses on the increasing environmental apprehensions and persistence of numerous organic contaminants so-called emerging contaminants (ECs), including biologically active elements from pharmaceutical source industries. Several types of diverse pharmaceutical-related compounds are being detected in environmental matrices and wastewater treatment units. Owing to this broader occurrence, transformation, and detection of pharmaceutical-related compounds in water matrices, people and legislative authorities are now more concerned about potential sources and ecological consequences of ECs. This is mainly because the free movement of ECs in water matrices is posing noteworthy adverse effects on human, aquatic animals, and naturally occurring plants, even at minimal concentrations. So far, several detection and treatment processes have been proposed and exploited against numerous pharmaceutical-related ECs. The useful and side effects of pharmaceutical-related compounds have been extensively inspected. Owing to this substantial research gap, the sources and environmental persistence of pharmaceutical-related ECs and their direct/indirect adverse effects have now been the topic of intensive studies. From the surface water perspective, wastewater treatment plants (WWTPs) are the major source of pharmaceutical-related ECs. The current chapter spotlights the widespread occurrence, numerous sources, and transportation fate of pharmaceutical-related ECs in water matrices.

Sewage sludge is a by-product of the sewage treatment plants. Because of its richness in nutrients and for several environmental and economic reasons, this waste by-product is widely used as a fertilizer for agricultural purposes under specific conditions. This practice might be hazardous since this waste includes many known and unknown non-biodegradable and harmful pollutants, especially emerging organic contaminants (EOCs), as well as cultivable and non-cultivable pathogens. The present work is aiming at (1) providing information on the nature of sludge in terms of persistent pollutants and cultivable and non-cultivable microbiota generated by the currently implemented treatment processes, (2) analyzing the consequences of the agricultural valorization on ecosystem biodiversity and soil fertility, and (3) addressing and discussing the economic, ethical, and environmental benefits or damage of this type of valorization. These issues need full consideration by policy makers regarding the agricultural use of this waste by-product in terms of irrigation with treated domestic wastewater or sludge land spreading as soil fertilizer and plant growth promoter.

The use of non-conventional water resources can help to mitigate water stress and can support the agricultural sector. Treated municipal wastewater is one of the most readily available alternative water resources, and its use in agriculture has been adopted to reduce fresh water usage in several countries, under their respective water quality regulations. This chapter reviews the results of past and current research on the reuse of treated wastewater (municipal and agro-industrial) for irrigation and the corresponding effects on soil and plant systems. Particular attention has been given to research efforts highlighting the effects of chemical-physical wastewater characteristics (e.g. nitrogen, phosphorus, potassium, sodium, and heavy metals) and the corresponding microbiological indicators (e.g. Escherichia coli and Salmonella) on irrigated crops and soils. The selection of irrigation methods is another topic discussed in this chapter. Drip and subsurface irrigation methods are considered the more suitable irrigation techniques to be used with treated wastewater; they minimise toxicity hazards for plants, reduce the contamination of edible crop products, and mitigate human health risks by minimising direct contact between wastewater and plant.

Pharmaceuticals originating from reclaimed wastewater or biosolid-, livestock manure- or sewage sludge-amended soils can enter crops by irrigation and fertilization. Generally, the putative uptake occurs through the plants’ roots and can lead to the bioaccumulation in different plant parts. The uptake and translocation therefore is dependent on multiple parameters, i.e. physicochemical properties of compounds, plant physiology and environmental factors. This book chapter combines a theoretical background on the main principles of uptake and translocation of pharmaceuticals by plants and a critical evaluation of current available literature, by analysing studies for the bioconcentration and translocation factors of different pharmaceutical groups in several plant species. Thereby, interesting results were obtained by looking at the translocation of various pharmaceuticals in radish and at cationic compounds in soil studies. Comparing the different studies, the relevance of testing not only high but also real environmental concentrations became obvious, since for some pharmaceuticals, higher uptake and translocation ratios were achieved with lower applied concentrations. Basic guidelines could provide a possibility to make scientific data more comparable and reliable and to avoid the exclusion of potential reasons for the missing uptake or translocation of pharmaceuticals. This book chapter provides recommendations for future research studies to generate more valid conclusions within the scientific community.

Wastewater (WW) reuse and biosolid application for vegetable crop culture is a practice applied worldwide. This strategy helps mitigate the pressure on water resources and improve the fertility of soil. Wastewater reuse is currently not included in chemical risk assessment, but its application has risk of potential accumulation of contaminants of emerging concern such as pharmaceutical active compounds (PhACs). In fact, this practice has caused the uptake of PhACs by plant and their subsequent entrance on the food chain. Residual quantities of contaminants may enter in soil, and they can be accumulated or percolated, consequently leading to contamination of groundwater. Herein, we report the main factors that play an important role on the accumulation of PhACs in soil after irrigation with treated wastewater. Limited data is actually available on the fate of PhACs in field studies because several processes are in competition for their dissipation including sorption and formation of non-extractable residues, leaching, as well as biotransformation. Consequently, an approach based on enantiomeric fractionation of chiral PhACs has been suggested to discriminate between biotic and abiotic dissipation processes.

The reuse of wastewater to meet increasing demands on freshwater resources coupled with the use of biosolids as soil amendments in agricultural landscapes provides many pathways for exposure to pharmaceuticals into the agroecosystem. Wastewater and both agricultural and municipal biosolids are known reservoirs for the potentially hundreds of pharmaceuticals that are in use throughout the world. Over the past 15 years, research has focussed on gaining an understanding of the extent of exposure, the fate and uptake of these compounds and the potential toxicological impacts these compounds may have once introduced. The agricultural system is a complex web of micro and macro fauna that includes microbes, fungi, invertebrates and plants which all may act as sinks for bioaccumulation and receptors for these biological active xenobiotic compounds. In this review, we describe how different experimental designs have been utilised to provide insights into the extent of uptake into plants and invertebrates, the mechanisms that govern this fate process and the evidence of biological effects that makes up our current understanding of pharmaceutical exposure in agricultural systems. We highlight the types of compounds as well as the model plant and invertebrate organisms that have been most studied. Furthermore, we discuss how geographical and economic drivers have influenced where research has been conducted and how this may bias our current understanding of pharmaceutical exposure risk as it relates to low- and middle-income countries.

With the increasing use of wastewater for irrigation of farmland, and thus the potential uptake and translocation of pharmaceuticals and their metabolites in crops, concerns about food safety are growing. After their uptake, plants are able to metabolize drugs to phase I, phase II, and phase III metabolites. Phase I reactions closely resemble those encountered in human drug metabolism, including oxidations, reductions, and hydrolysis. Phase II reactions, in turn, encompass conjugations with glutathione, carbohydrates, malonic acid, and amino acids. In phase III, these conjugates are transported and stored in the vacuole or bound to the cell wall. Pharmaceutical metabolism in plants has been investigated by using different approaches, namely, the use of whole plants grown in soil or hydroponic cultures, the use of plant tissues, and the incubation of specific plant cell suspensions. While studies relying on whole plants require long growth periods and more complex analytical procedures to isolate and detect metabolites, they constitute more realistic scenarios with the ability to determine site-specific metabolism and the translocation within the plant. The advantage of in vitro studies lies in their rapid setup. Recent advances in plant-microbiota investigations have shown that the plant microbiome modulates the response of the plant towards pharmaceuticals. Rhizospheric and endophytic bacteria can directly contribute to pharmaceutical metabolism and influence plant uptake and translocation of pharmaceuticals and their metabolites. Additionally, they can have beneficial properties for the host, contributing to plant health and fitness. This chapter gives an overview of human and plant drug metabolism followed by a comparison of different models used to identify pharmaceutical metabolites and their metabolic pathways in plants. A description of the mechanisms and reactions originating these metabolites is concisely presented. Finally, the role of the microbiome is critically discussed with examples of synergies between plants and their associated microbiota for pharmaceutical degradation.

The use of reclaimed water in crop irrigation helps to mitigate water shortage. The fertilization of arable soils with sewage sludge, biosolids, or livestock manure reduces extensive application of synthetic fertilizers. However, both practices lead to the introduction of pharmaceutical active compounds (PhACs) in arable soil, known to host a wide range of living organisms, including microorganisms which are supporting numerous ecosystem services. In soils, the fate of PhACs is governed by different abiotic and biotic processes. Among them, soil sorption and microbial transformation are the most important ones and determine the fate, occurrence, and dispersion of PhACs into the different compartments of the environment. The presence of PhACs in soils can compromise the abundance, diversity, and activity of the soil microbial community which is one of the key players in a range of soil ecosystem services. This chapter reviews the current knowledge of the effects of PhACs, commonly found in wastewater effluents and derived organic fertilizers, on the soil microbial community.

Soil-dwelling naturally occurring earthworms (e.g. Lumbricus terrestris) are valuable sentinels in soil pollution monitoring for their ecological role but also because they have shown to be sensitive to environmental contaminants. However, most laboratory studies have adopted epigeic earthworms as models (Eisenia spp.) in acute toxicity testing. In soil chronic toxicity assessment, it is essential to include sublethal responses that can have direct implications on species performance, reproduction and behaviour and thus be of ecological significance. In this sense, some biochemical biomarkers are regarded as early warning signals of further ecological consequences. Amongst those most frequently considered are specific responses to certain chemicals (e.g. metallothionein induction to metal exposure) but also those related to oxidative homeostasis of the organisms because prolonged stress may lead to adverse effects at the individual level (disruption of immune system, altered growth and reproduction). Biomarker measures can be applied in specific tissues, but, for methodological constraints, the consideration of the whole animal simplifies protocols and, once validated, they are informative and integrative. The use of non-destructive tissues (e.g. coelomocytes) that do not require sacrifice, the incorporation of “omic” disciplines and recent technical advances in metabolite identification are all encouraged to be incorporated into toxicity evaluation.

Constructed wetlands are one of the most often applied nature-based solutions for water management. This ecotechnology is widely accepted due to its robustness to treat wastewater. The assessment of organic carbon and nutrients removal for conventional wastewater treatment has been documented for nearly 70 years. In the recent decade, interest has increased in regard to their performance to treat water contaminated with pharmaceuticals. In 2020 we have passed 200 publications on the latter. Therefore, there is a fair amount of knowledge available to discuss the applicability of constructed wetlands to control the emission of pharmaceuticals. The current chapter aims to (1) provide an insight to the performance of constructed wetlands under a variety of configurations and design options for the removal of pharmaceuticals; (2) discuss removal processes, namely, plant and biological-driven biodegradation, the challenges in its application and reproducibility, the knowledge gaps and the future trends; and (3) link constructed wetland usage and developments with the recent trends of nature-based solution and phytoremediation implementation towards a green transition.

Pharmaceuticals have been becoming a major concern of environmental pollution since the beginning of the century. The ways in which these contaminants are introduced into the environment are very different, but almost always associated with wastewater. In fact, current wastewater treatment plants are not designed for the removal of pharmaceutical products. Indeed, the problem of water scarcity has played an important role in the introduction of pharmaceutical products into the environment, particularly in the agricultural sector. Because of the drought, more and more countries are resorting to the use of treated wastewater to irrigate vegetables for human consumption. Consequently, the reuse of wastewater in agriculture constitutes a continuous introduction of these molecules into the soil.

The effects of this practice are not entirely clear. However, the probability that these compounds can enter the food chain directly is high. In fact, through radical absorption, plants could uptake pharmaceuticals from soil and water, leading to the accumulation of drugs in the tissues.

The development of analytical methods of solid matrices such as soil or plant tissues requires substantial work due to the great complexity of the matrices and the differences between the physico-chemical properties of analytes of interest. Several multi-class methods have recently been developed to determine a large number of pharmaceutical products in soil or plants using different extraction techniques.

This chapter addresses to list all the analytical procedures published so far used for the extraction and analysis of pharmaceutical products from plant tissues and from the soil irrigated with treated wastewater.

The present chapter gives an overview of analytical methodologies employed for the identification and quantitation of metabolites formed in plants or plant cell cultures from drugs and personal care products after uptake from water or soil. Important aspects like experimental approaches for plant growing, extraction of the investigated analytes from plants, preconcentration strategies, and final analytical techniques allowing the proposal of (at least tentative) structures for drug-related metabolites are discussed. Special emphasis is also set on the elucidation of translocation processes by analyzing different plant parts. In one table, a comprehensive overview of the current state of knowledge available from the literature is given, with respect to the topics listed above.

During the course of this book, we have witnessed how wastewater represents an important agronomic resource especially in areas of the world affected by drought or where availability is usually limited. However, this practice raises many fears not only in the environmental field but especially in the case of food safety. In fact, wastewater represents the main source of diffusion of pharmaceutical residues (including degradation products and metabolites) in the aquatic and terrestrial environment. For assessing the occurrence of drugs and related substances, sensitive analytical methods have recently become available.