Elsevier

Environmental Pollution

Volume 267, December 2020, 115370
Environmental Pollution

Review
Non-steroidal anti-inflammatory drugs in the environment: Where were we and how far we have come?

https://doi.org/10.1016/j.envpol.2020.115370Get rights and content

Highlights

  • High use and scarce knowledge on NSAIDs fate, disposal and ecotoxicity creates crisis.

  • Varied NSAID concentration enter aquatic and terrestrial environment by main routes.

  • Steady NSAID leak as initial/active metabolite exerts toxic effect on organisms.

  • NSAIDs accumulation triggers potential risks for public health and non-target organisms.

Abstract

Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most well-known pharmaceuticals with a broad scope of properties that are widely used in human and veterinary medicine. Because of their extensive utilization, NSAIDs are commonly identified in the environment as trace emerging contaminants. Regardless of vast experience with these drugs, NSAIDs are full of contradictions that trigger major concerns for environmental researchers. A limited understanding on NSAID’s occurrence, distribution and eco-toxicological effects have led to an escalated dilemma in the last decade. Thus, a broad-spectrum study covering all aspects of occurrence, detection and removal is required to meet the fundamental levels of knowledge on the effects of NSAIDs in all exposed environmental aspects. Therefore, this paper focuses on classifying the sources and entry points of residual NSAIDs. Further, detecting and regulating their concentrations in both input streams and receiving environments, along with the removal processes of this specific class of emerging compounds, in the direction of developing a management policy is comprehensively reviewed.

Introduction

In the recent decade, there has been an increasing interest in emerging contaminants (ECs) including, pharmaceutically active compounds, endocrine-disrupting chemicals and personal care products (PCPs) (Boix et al., 2016; Tran et al., 2018) (Petrie et al., 2015). The main threat of mentioned classes of ECs is due to missing information, regarding their environmental and human toxicological effects, as well as an understudied area of detection, analysis and removal methods (Yu et al., 2011). The initial classification of pharmaceuticals and PCPs as major and concerning pollutants was proposed by Daughton and Ternes (1999) (Daughton and Ternes, 1999), which was followed by advancements in analytical procedures and the growing development of environmental matrices. An increased concern in recent years is directed towards active pharmaceutical ingredients (APIs), that are identified at trace level in surface waters, sewage and wastewater treatment plants (WWTPs) effluents which eventually returns to human bodies (Daughton and Ternes, 1999), due to their high stability in chemical structure as well as highly active functional molecule groups (Tyumina et al., 2020). Due to the lack of knowledge on the analytical techniques in detection, these groups of emerging contaminants, enter the environment without any control or regulation (Barroso et al., 2019). The non-steroidal anti-inflammatory pharmaceuticals (NSAIDs) are one of the most frequently used pharmaceuticals internationally, and listed among the top 10 persistent pollutants (Green, 2001). Among the NSAIDs, the most recurrently detected in the environment includes diclofenac (DCF), ibuprofen (IBP) and naproxen (NPX) recognized as potential ECs with high-octanol partition coefficient and low pKa values (Table 1). These specific drugs reduce inflammation and pain by blocking COX enzymes and prostaglandin production. Standard biological actions and body maintenance roles are directly related to cyclooxygenase (COX) activity and prostaglandins, wherein analgesia and anti-inflammation are achieved through induction. Prostaglandins (lipid autacoids resulting from arachidonic acids) are strong intermediaries of inflammation that cause edema, pain, and vasodilation. The mechanism of action of these drugs is indicated in supplementary data (Figure S1). Consequently, a great capacity to passively diffuse through biological membranes, with an elevated persistence in aquatic environments, is observed in these pharmaceuticals (Almeida et al., 2017; Green, 2001; Jiang et al., 2017).

This review aims to drive the focus on adopting a novel challenge-driven approach towards determination, monitoring and removal of NSAIDs. Previous studies investigated the occurrence, fate and removal of EC’s and pharmaceuticals in general, however, the elimination of NSAIDs residuals in the environment demands exclusive research (Feng et al., 2013) (Tanwar et al., 2015) (Tijani et al., 2013). This paper summarizes current knowledge on determination, detection, fate and occurrence along with the removal of NSAIDs in the environment particularly in WWTPs, with a great emphasis on innovative and advanced tools and technologies. Additionally, previous reviews, lack a focus on current policies and regulations on the usage and release of NSAIDs in the environment. This review paper investigates the available data and policies to formulate guidance for further regulation of NSAIDs in the environment. The final objective was to recognize knowledge scarcities and put forward research guidelines for upcoming investigations.

Section snippets

Wastewater (WW), surface water, groundwater and drinking water

NSAIDs are commonly used across the world and have been released in a range of millions of tons back into the environment with high concentrations of these pollutants accumulated in treatment systems (Fent et al., 2006) (Żur et al., 2018) (Li, 2014). The concentration levels vary from one country to another based on the drug consumption and usage pattern, population and efficiency of treatment plants (Tijani et al., 2013). Moreover, there is comparable difference between number of studies on

Biological samples

In general, drug analysis follows a three-step procedure: extraction-separation-detection. Several studies mark the extraction/sample pretreatment phase of NSAIDs analysis as complicated, especially in the case of biological fluids, due to the complex nature of samples and the relatively low concentration of target analytes (Farajzadeh et al., 2015), (Martinez-Sena et al., 2016), (Sarafraz-Yazdi et al., 2012). Furthermore, multi-residue analysis of drugs is likewise challenging because of the

Policy on EC management and related constraining circumstances

The postponement of regulations and laws concerning the assessment of adverse environmental and health effects of pharmaceutical as emerging pollutants have drawn attention by concerned parties, although regulations have never kept the pace of industrial and technological developments specifically in the case of groundwater (Naidu et al., 2016).

Several matters are holding down the policymaking process such as lack of knowledge and regulations as well as increasing the expansion of new

Discussion and future work

NSAIDs presence in any aquatic or soil environment has the potential to alter the diversity, biomass composition, biochemical reactions, metabolic and enzymatic activity of the microbiological community (Cycon et al., 2016), which inhibits the presence of indigenous species and alters key ecological processes. This review shows the limited data and studies available on NSAIDs as emerging contaminants and the other hand, the crucial need to develop the dataset for human health risk assessment

Conclusion

NSAIDs have been used as anti-inflammatory drugs and have been present in the aquatic and solid environmental matrices for decades and life has been exposing to it. Recently, the detection, quantification and removal of these compounds have grown by excessive research efforts, devoted to study the occurrence of ECs and the effective removal methods. However, for the prediction of these micropollutant impacts on the environment, comprehensive modeling of NSAID fate is required. Overall,

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

The authors appreciate recognizing the Ontario Graduate Scholarship (OGS), James and Joanne Love Chair in Environmental Engineering and Seed Fund, York University, Toronto, ON, Canada for their endless support and interest at each point of this research.

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