360-Degree Waste Management, Volume 2: Biomedical, Pharmaceutical, Industrial Waste, and Remediation

By Bharat Bhanvase and Sanjay J. Dhoble

360 Degree Waste Management, Volume Two: Biomedical, Pharmaceutical, and Industrial Waste and Remediation presents an interdisciplinary approach to understanding various types of biomedical, pharmaceutical, and industrial waste, including their origin, management, recycling, disposal, effects on ecosystems, and social and economic impacts. By applying the concepts of sustainable, affordable and integrated approaches for the improvement of waste management, the book confronts social, economic and environmental challenges. Thus, researchers, waste managers and environmental engineers will find critical information to identify long-term answers to problems of waste management that require complex understanding and analysis.Presenting key concepts in the management of biomedical and industrial waste, Volume Two of this two volume series includes aspects on microbiology of waste management, advanced treatment processes, environmental impacts, technological developments, economics of waste management and future implications.

• Provides a critical assessment of economic, social and environmental challenges due to solid wastes, highlighting sustainable management approach
• Describes various factors to be considered while developing waste management strategies, including techniques for reuse, reduce, recycle or recovery of solid waste and management of other wastes, such as wastes from pharmaceuticals, aluminum industry, heavy metal, and other metallurgical waste
• Addresses contemporary issues such as the transformation of waste into value-added products
• Presents an interdisciplinary approach to the management of various types of biomedical, pharmaceutical and industrial waste

• Language: English
• Publisher: Elsevier Science
• Release date: Jul 1, 2023
• ISBN: 9780323910392

Book preview

Section 1

Biomedical and pharmaceutical waste

Outline

Chapter 1 Pharmaceutical waste: an emerging threat to the ecosystem

2 Evolving toxicological measurements for pharmaceutical waste-induced health hazards

3 Domestic pharmaceutical and personal care products waste: are we wise enough to deal with it?

4 Pharmaceutical waste: a health risk for humans

5 Development strategies for pharmaceutical waste management: in view of healthcare perspectives

6 Processes for the treatment of biomedical wastes: challenges and issues

Chapter 1

Pharmaceutical waste: an emerging threat to the ecosystem

Anmol Dhawande¹*, Snehal Moon¹*, Vijay Kale², Anil M. Pethe³ and Nishikant A. Raut¹,    ¹Department of Pharmaceutical Sciences, Rashtrasant Tukadoji Maharaj Nagpur University, Nagpur, Maharashtra, India,    ²College of Pharmacy, Roseman University of Health Sciences, South Jordan, UT, United States,    ³Datta Meghe College of Pharmacy, Datta Meghe Institute of Higher Education & Research, Deemed University, Sawangi (Meghe), Wardha, Maharashtra, India

Abstract

Drugs or medicaments are substances that are consumed for their therapeutic uses, and after producing their biological action, they are excreted with or without metabolizing in the body. Pharmaceutical and therapeutic agents are considered a boon for humans and other living beings. However, there is another side to this blessing, which is still in the dark and may become a curse for all living organisms on the planet. The fate of active pharmaceutical ingredients, solvents, intermediates, and raw materials after the completion of their desired functions, is a matter of concern. Discarded, expired, or unwanted drugs are usually thrown out as garbage. What happens to these drugs after they are disposed of? Do they degrade or percolate? If they do not degrade but only percolate, where they do they go after percolation? What are the effects of the remains of these drugs on the environment and living organisms? The answers to almost all the questions lead us to the impact of pharmaceutical waste on the ecosystem. This chapter is an attempt to review the emerging threats to the ecosystem, which may enable us to identify the gaps in suggesting measures for future analysis.

Keywords

Pharmaceutical wastes; ecosystem; hazards; medicines; drugs

1.1 Introduction

Pharmaceutical waste most often implies to the waste generated by pharmaceutical industries and hospitals. However, since the 1980s, pharmaceuticals have been recognized as chemical pollutants [1]. Drugs are discovered for the diagnosis, treatment, or prevention of existing and new diseases. They are developed to give better results and are manufactured and marketed by the ever-growing pharmaceutical industries. Various aspects of the pharmaceutical industry, such as efficacy, safety, analysis, patenting, and marketing, are controlled and governed by laws and regulations imposed by regulatory agencies, such as Food and Drug Administration (FDA). Pharmaceutical industries are associated with several operations, including the synthesis and manufacturing of active pharmaceutical ingredients (APIs), excipients, formulation, and development of suitable dosage for API, followed by their manufacturing and the analysis of raw materials as well as the finished pharmaceutical products. Although pharmaceuticals are known for their large production and market in the world, their fate after their intended use is undefined. Pharmaceuticals tend to prove their existence even in the form of waste. Pharmaceutical wastes are in various forms based on their use and sources. Waste management, especially in the pharmaceutical sector, needs urgent attention as the consequences are much more severe and beyond contemplation.

The pharmaceutical sector is among the largest growing healthcare sectors, contributing significantly to the global economy. Though pharmaceuticals, which contain active ingredients and excipients, are produced for their beneficial effects in humans as well as animals, they are also known to cause several adverse effects. Right from the initial stages of production/synthesis to the final stage as excreta or waste as expired medicines, pharmaceuticals have an adverse impact on the environment and human health. The size or scale of the global demand and supply of pharmaceuticals is enormous, while the waste generation is also gigantic. Pharmaceutical wastes are not only generated by the pharmaceutical industry but also by hospitals, patients, veterinary sectors, and agricultural areas in various forms. Improper disposal and inappropriate management of pharmaceutical waste lead to their introduction into the environment in the form of soil contamination, surface water bodies, groundwater, and air [2].

An interesting study by Kolpin et al. [3]. investigated the appearance of various hormones, pharmaceutical ingredients, and other organic compounds in streams near urbanization or livestock-producing units. In the United States, samples were taken from about 139 streams from 30 different states, and the study demonstrated that about 80% of the total streams sampled were found to be contaminated with at least one organic wastewater contaminant (OWC) of the 95 known contaminants, including pharmaceuticals. Most of the OWCs (82) were found in at least one stream sample, and 13% of the streams contained more than 20 OWCs. Many of the OWCs were pharmaceuticals belonging to common prescription and nonprescription drugs. In a geological survey of Minnesota wastewater, surface, ground, and drinking water, OWCs were found in 90% of the samples. The highest levels detected were of prescription drugs, nonprescription drugs, and antibiotics [3]. Although pharmaceutical contaminants have not been found at therapeutic levels, they have potentially adverse consequences, including water quality degradation, antibiotic resistance, endocrine disruption, and negative social implications for the cleanliness of the water.

The removal of waste drugs has been a substantially less obtrusive, yet no less significant, issue. During regular curriculum delivery in academics, almost none of the healthcare professionals, including doctors, pharmacists, and nurses, receive training related to the management of waste (both general and biomedical). On the other hand, personnel handling waste management or environmental safety managers are not acquainted with the drugs, their APIs, and their formulations. Therefore it is imperative to include appropriate training in the curriculum of medical, pharmacy, nursing, and waste management. This chapter aims to highlight the plausible hazards of pharmaceutical waste to the environment and ecosystem.

1.2 Background

Attempts to minimize or regulate the disposal of pharmaceutical waste are not new. The Resource Conservation and Recovery Act (RCRA), established in 1976, governs the management of solid and hazardous waste generated within the United States. RCRA also authorizes the Environmental Protection Agency (EPA) to regulate and track the disposal of solid waste, and set forth strict rules for facilities that generate, transport, store, and dispose of hazardous waste. A number of pharmaceuticals meet the definition of hazardous waste under RCRA, while EPA and some state environmental agencies are now seeking healthcare facilities to identify, segregate, contain, and appropriately label, store, transport, and dispose off these hazardous wastes in compliance with RCRA regulations. As a result of this focus on the part of regulators, surveyors for the Joint Commission are also including pharmaceutical waste management in their survey questions [4]. Some regulatory agencies that supervise pharmaceutical waste management are listed below:

1.3 Definition of pharmaceutical waste

In pharmaceuticals, a drug is defined as any substance of natural or synthetic origin used to treat, cure, mitigate, prevent, or even diagnose disease or disorders in living beings. On the same ground, pharmaceutical waste is defined as substances of natural or synthetic origin, single or in a combination of chemicals or biological products, used in the treatment, cure, care, mitigation, prevention, and/or diagnosis of diseases or disorders in living beings but of no use due to the expiration of their shelf life (or if the date of expiration is not known), as well as being unwanted, contaminated, discontinued, or discarded drugs. When drugs are prescribed for any ailment, acute or chronic, or even for prophylactic applications, a portion of the drug is responsible for the biological activity and gets metabolized, whereas a portion of the drug may remain accumulated in the body, and the rest of it is excreted. The metabolites of the parent drugs and the nonmetabolized drugs are excreted from the body through urine and fecal matter, which enter the environment directly or through sewage or treated wastewater. The unused or expired drug reaches the environment as pharmaceutical waste in the form of landfills or drainage, posing a threat to the ecosystem.

1.4 Classification of pharmaceutical wastes

The classification of pharmaceutical waste depends on the nature of the materials and is usually classified broadly into three types:

1. Hazardous waste

2. Nonhazardous waste

3. Chemotherapy waste

1.4.1 Hazardous waste

Wastes that may be potentially hazardous to humans, animals, and the environment, and have their origin somewhere in pharmaceuticals, are considered pharmaceutical hazardous waste. However, there should be a clear-cut distinction between medical waste and pharmaceutical waste, as this may create confusion with regard to appropriate disposal guidelines. There are several differences, while considering disposal procedures for medical waste placed in red bags referred to as red bag waste streams and other hazardous waste as RCRA (Resource Conservation and Recovery Act) waste streams [5]. An effective hazardous waste management approach should consider environmental impacts as the first line and ultimate goal, eventually protecting human and animal health.

Pharmaceuticals, when treated, transported, disposed off, or stored inappropriately as recommended by the manufacturers or regulating agencies, may cause a serious hazard to the environment and health or may even lead to the death of human beings or other animals. Such kinds of drugs are highly regulated and such drug providers must implement proper methods of disposing of them. Pharmaceutical waste contaminates the environment in several ways mainly due to careless and improper disposal. Pharmaceutical wastes, mostly in the form of chemicals, reach the environment through numerous ways, as mentioned below [6]:

In many developing countries, medication samples for physician use only are often found across the roadsides [7].

Hazardous waste may include waste in any state of matter, such as solids, liquids, and gases categorized based on either their sources or according to EPA’s 40 CFR Part 261, as shown in Fig. 1–1. Several different types of hazardous wastes are generated by the pharmaceutical industries, and the regulatory agencies/acts/commissions in respective areas of the world regulate them. Moreover, the Basel Convention (World Environmental Agreement on Wastes) was signed by 53 signatories on March 22, 1989, for the control of transboundary movements of hazardous wastes and their disposal.

Figure 1–1 Various ways in which drugs contribute to environmental pollution.

Hazardous wastes can be classified into three categories:

1. Listed hazardous pharmaceutical wastes

2. Characteristic hazardous wastes

3. Miscellaneous hazardous wastes

1.4.1.1 Listed hazardous pharmaceutical wastes

Several pharmaceutical wastes are listed by RCRA as hazardous wastes, denoted as F, K, P, and U lists to categorize various types of wastes. The F and K lists are not specific but include a few hazardous pharmaceutical waste [8].

The F-list: The F-list includes hazardous wastes from manufacturing and industrial processes and falls within the ambit of certain categories mentioned below:

The use of solvent procedures in diagnostic laboratories is one of the major sources of spent solvents in the nonhalogenated category of F-listed wastes, which mostly include the solvents listed below:

The K-list: The K-list comprises hazardous wastes originating from specific production industries, which include the manufacturing industries of organic chemicals and veterinary pharmaceuticals.

The P-list: The chemicals listed under the P-list are acutely toxic and commercially available, which include nicotine, nitroglycerin, phentermine, epinephrine, physostigmine, and warfarin, wherein, both the chemical compound and its container are regarded as hazardous and essentially disposed of according to RCRA guidelines in an approved container.

The U-list: The chemicals listed under the U-list cover several pharmaceuticals in a broad range, which include chloral hydrate, lindane, phenol, and some antineoplastic waste. All these chemicals, which are the sole active ingredients, are required to be strictly regulated by the hazardous waste norms. However, in practice, they are disposed of neither as sole active ingredients nor as U-listed chemicals.

1.4.1.2 Characteristic hazardous wastes

Characteristic hazardous wastes are pharmaceuticals with characteristic hazardous properties as follows:

1. Ignitability

2. Reactivity

3. Corrosivity

4. Toxicity

The characteristic wastes are also called D-list according to the RCRA.

1.4.1.2.1 Ignitability

This is the characteristic of substances that catch fire under specified conditions. These substances are usually liquid wastes having flash points <60°C, including some compressed gases, oxidizers, and some nonliquids, which can cause fire on ignition. Pharmaceutical wastes, having this characteristic, and containing >24% alcohol or gel bases with flash points <60°C, including benzoin, rubbing alcohol (iso-propanol), some topical preparations, and paclitaxel, fall into this category.

1.4.1.2.2 Corrosivity

Waste materials possessing the characteristic of causing erosion or corrosion of materials due to the effect of chemicals with an extreme pH (usually >2 or <12.5) are typically considered corrosive wastes. Liquids with such pH levels can cause corrosion of steel and may lead to potential damage. The chemicals used in compounding, such as strong acids and bases, are examples of corrosive pharmaceuticals.

1.4.1.2.3 Reactivity

This is the characteristic of substances undergoing chemical reactions with other molecules or among the same molecules. These wastes are generally unstable, undergoing rigorous changes, violently reacting with water, or generating toxic gases, fumes, or vapors when mixed with water, or detonating when heated. These reactions can cause significant harm to human beings and the surrounding environment.

1.4.1.2.4 Toxicity

This is the characteristic of chemical substances (alone or in a mixture) to cause harm or damage to the living beings irrespective of whether they are bacteria, animals, or plants. Such toxic substances cause harm to living beings when they come into contact with them internally (when consumed) or externally. These toxic pharmaceutical wastes usually contain heavy metals, such as arsenic, barium, cadmium, chromium, mercury, selenium, and silver, as well as some nonmetals, such as chloroform, lindane, and m-cresol, whose concentration exceed the permissible limits prescribed by regulating agencies. Although rare, it has also been reported that some diluents or preservatives, apart from the API, in compounded or commercial formulations, cause toxicity.

1.4.1.3 Miscellaneous hazardous wastes

Wastes that are not listed and do not exhibit a characteristic of hazardous waste are considered miscellaneous wastes, or sometimes referred to as solid wastes. Solid wastes should be discarded according to state and/or local regulations, including regulated medical waste requirements [8].

1.4.1.3.1 Controlled pharmaceuticals

Controlled pharmaceuticals are a special class of medicines that require controlled or regulated use. These chemicals are toxic with a narrow therapeutic index or the drugs that are highly addictive and often abused. There are certain laid-down procedures for the disposal of such controlled pharmaceuticals, which should meet the standard protocol of disposal of controlled pharmaceuticals. These substances are usually collected onsite in special containers and are then combined, examined, accounted for, packed, and dispatched to appropriate disposal centers or authorized agencies for final disposal as per the protocol.

1.4.1.3.2 Agricultural use pharmaceuticals

The drugs or pharmaceuticals used to prevent or treat microbial infections in crops due to various viruses, bacteria, and fungi are agricultural use pharmaceuticals. These pharmaceuticals are also used as insecticides and pesticides on the crops. The treatment usually includes spraying solutions of such agricultural use chemicals on crops. The sprayed pharmaceuticals usually end up settling down on the crop as well as on the soil. Apart from it, the sprayed chemicals become airborne and contaminate nearby places, causing harm to the ecosystem. The pharmaceuticals used in agriculture are mostly toxic to humans, animals, and birds polluting the soil, air, and water additionally.

1.4.2 Nonhazardous waste

On an average, 5%–15% of the total waste generated at healthcare facilities is classified as hazardous waste, while the rest of the waste regarded as having insignificant hazardous properties is classified as nonhazardous pharmaceutical waste. However, considering nonhazardous pharmaceuticals as nonhazardous waste is a misnomer. It does not render them safe; it only signifies that these substances/materials fall below the limit identified for substances to be categorized as hazardous waste. There is a thin line between hazardous and nonhazardous pharmaceutical waste which is often blurred. Any addition or removal of a component from the nonhazardous waste may make it harmful. In such situations, usually the prescribed limit of a particular component reaches its threshold, resulting in hazardous effects and necessitating a change in the waste management option.

Some ingredients in pharmaceutical preparations are considered pharmacologically inert, with no pharmacological activity, and are called as excipients. These products are used as replenishers with no significant pharmacological properties. However, they are administered and controlled by medical practitioners. For example, products such as dextrose or sodium chloride solutions may get mixed with or added to other substances requiring evaluation before being disposed of as containing hazardous properties.

There are some pharmaceuticals that are considered waste but are produced in lower amounts and can be classified as follows:

1. Over-the-counter (OTC) pharmaceuticals

2. Nonhazardous prescription pharmaceuticals

3. Veterinary use pharmaceuticals

1.4.2.1 Over-the-counter pharmaceuticals

Some general-purpose medicines are sold over the counter, mostly without a prescription from a registered medical practitioner. To treat common ailments, such as cough and cold, headache, acidity or acid reflux, fever, body ache, and allergic reactions, along with other health problems, people ask for these medications over the counter. Such unused medicines are usually discarded in the trash, flushed into the toilet or sink, or left negligently. The trashed medicines contaminate landfills, whereas the flushed medicines cause disruption of sewage treatment processes and the surface water ecology of microorganisms. The medicines left behind negligently may be accidentally consumed by children or inappropriately consumed by adults, leading to adverse drug reactions. So, it is highly recommended that such OTC medicines or pharmaceuticals be disposed off following the guidelines of regulatory agencies and appropriate awareness should be spread among the general public.

1.4.2.2 Nonhazardous prescription pharmaceuticals

Nonhazardous pharmaceuticals are medicines prescribed by physicians for treating various ailments. Though these medicines are classified under the nonhazardous category, they may be potentially hazardous to the environment and the whole ecosystem if not disposed of properly. According to the regulations, such unused medicines should not be disposed off in regular trash. They should be deposited at the nearest medical facility or returned to the manufacturer for regulated disposal as medical waste as per the guidelines of the regulatory agencies.

1.4.2.3 Veterinary use pharmaceuticals

This category includes pharmaceuticals administered to or sprayed on livestock and pet animals, such as cats, dogs, and cattle. In developed countries there are dedicated specialized hospitals and veterinary clinics for pet animals as well as for livestock. However, in underdeveloped or developing countries veterinary care and treatment for veterinary illnesses, as well as prevention of infectious diseases are advised at home. After the treatment, the unused or discarded drugs are mostly disposed off in the environment in the form of landfills, causing hazard to the ecosystem.

1.4.3 Chemotherapy wastes

Chemotherapy drugs, used for the treatment of cancers, are chemicals of cytotoxic nature, which are considered to be very hazardous and their handling requires special care. However, most of these drugs are flushed into the drainage carelessly, although they are considered dangerous and hazardous [9]https://www.malsparo.com/chemotherapy.htm.

The waste generated from the handling of chemotherapy drugs is also dangerous waste, which makes up approximately 5% of the total waste. Most chemotherapy agents are dispensed in the form of aqueous solutions, usually prepared in the hospital, contaminating the containers, disposables, and equipment used for the preparation. Some of the contaminated equipment are cleaned and reused while generating hazardous waste in the form of wash solutions. The materials used during the handling of chemotherapeutic agents that cannot be reused are required to be disposed off as hazardous waste according to regulatory guidelines [10].

Chemotherapy wastes are further differentiated as trace chemotherapy and bulk chemotherapy waste.

1.4.3.1 Trace chemotherapy waste

Paraphernalia used during chemotherapy is considered trace chemotherapy waste. The manageable trace chemotherapy waste listed by RCRA includes empty drug vials, IV bags, tubing, syringes, gloves, gowns, wipes, and other items associated with the usual handling, preparation, and thereafter administration of chemotherapy agents. The list also includes wipes and other materials employed for regular cleaning and decontamination of biosafety cabinets and glove boxes. However, since these wastes do not meet the requirement to be called hazardous, and fall under the category of RCRA empty with no strict regulatory guidelines, most of the time they are disposed off as solid waste. As these chemotherapy agents are cytotoxic in nature, the trace chemotherapy wastes may also create a threat to living beings and the environment. Considering this, some of the socially responsible healthcare facilities are treating trace chemotherapy waste preventing them to be disposed off as solid waste. If trace chemotherapy wastes are treated along with infectious wastes, which are usually treated with certain disinfectant chemicals, microwaved, or autoclaved, such methods will not destroy the cytotoxic properties of trace chemotherapy waste. Trace chemotherapy wastes are required to be separated from infectious waste and then incinerated to ensure the complete degradation of chemicals.

In order to manage trace chemotherapy waste, the following suggestions are proposed by various regulatory agencies:

• All used empty containers, including vials and syringes, and other items such as ports, IV bags, central venous access devices, etc., are ensured to be emptied to be considered trace chemotherapy waste and should be placed in waste containers for incineration.

• Contaminated PPE, such as gloves, gowns, goggles, wipes, and tubing, which are employed during handling chemotherapeutic agents should be placed in waste containers for incineration.

• Needles used for injecting chemotherapeutic agents must be discarded in designated sharps containers and shall be disposed of according to guidelines.

1.4.3.2 Bulk chemotherapy waste

Chemotherapy waste that does not fall under the category of trace or RCRA empty, which may remain as unused formulations of chemotherapeutic agents in IV bags, is considered bulk chemotherapy waste and required to be handled as hazardous waste. Several chemotherapy agents have not been included in the list of hazardous substances recommended by regulatory agencies. Considering them as hazardous, it is strongly recommended to handle such waste with utmost care for the safety of the healthcare and waste management workers.

To manage the bulk chemotherapy waste, the following suggestions are proposed by regulatory agencies:

• All containers that hold any amount of liquid (except residual amount) should be handled as hazardous waste, and the entire container (syringe, vial, IV bag, etc.) should be placed in the container designated for bulk hazardous waste to assure proper disposal.

• Overtly contaminated PPE, such as gloves, gowns, and goggles, and spill clean-up material, such as pads, rags, towels, and wipes, contaminated with chemotherapy agents during preparation or administration, should be handled as hazardous waste, and the entire material should be placed in the container designated for bulk hazardous waste to assure proper disposal.

• The unused formulations of chemotherapy agents in IV bags should not be drained or placed along with the solid waste. They should be disposed off in the designated infectious waste containers or incinerated as medical or municipal waste.

1.5 Scenario

In the field of pharmaceutical sciences, there are more than 20,000 APIs formulated into various dosage forms, such as oral, topical, and parenteral. The APIs affect both the biotic and abiotic systems and eventually randomize into the environment through the food chain, water bodies, sludges, and sewage [11,12]. The use of pharmaceuticals is increasing day by day for humans as well as for animals, and it has been reported that annual antimicrobial consumption reached about 100,000 tons [13]. It has also been reported that the levels of antibiotics and estrogenic hormones in the environment have increased so much that they are now on the EPA Drinking Water Contaminant Candidate List [11].

The reason for noneco-friendly disposal of pharmaceuticals in the environment or water bodies is the cost involved, which is mostly higher than the cost of manufacturing. Therefore, to reduce expenditure on the disposal of pharmaceutical waste, commercial entities (mostly from Asian countries) dump hazardous pharmaceutical waste in landfills or into water bodies [14]. In the United States the expenditure for disposing of pharmaceutical waste by incineration is estimated to be $4.4 to $8.2 million [15] whereas in India it costs about $2.1 million (about 0.5%–2.0% of total sales) [16]. The disease burden due to environmental hazards is estimated to be around 25% worldwide, while it is around 35% in Sub-Saharan Africa [17,18]. An extensive investigation for estimating the concentration of pharmaceuticals in the environment was performed by sampling over 123,761 sites worldwide [19] and it is clear that pharmaceuticals, along with personal care products, are adversely affecting the environment [11].

Several pharmaceutical industries are responsible for the generation of hazardous effluents, such as solids as well as biodegradable and nondegradable waste as a result of a variety of manufacturing processes. The effluents from these manufacturing industries are usually treated and then released into waterways and streams, which is evident from the physical-chemical analysis of the effluents. Most of these analysis reports comply with the standards prescribed by various governing/regulating agencies, however, the wastewater oxygen content and the dissolved and suspended solids greatly affect the ecosystem.

Regulations:

1.6 Impact of pharmaceutical waste on ecosystem and disposal methods

Pharmaceuticals, such as restoratives, analgesics, antihistamines, antibiotics, and hormones, are commonly found in groundwater receiving inputs from livestock waste or municipal wastewater discharges [20] More than 4000 pharmaceuticals are in the market [21] which are mostly formulated for human or animal diagnosis and treatment, and are delineated as biologically active. Pharmaceuticals are common contaminants in the aquatic ecosystem, usually occurring in very low concentrations (ng/L to μg/L), and the analytical methods to measure concentrations of several pharmaceuticals in the environment have been well developed [20]. Globally, a widespread range of pharmaceuticals have been detected in surface water, and the conceivable biological activities are required to be assessed, which will be useful in understanding the composite influence on the aquatic ecosystem. This is a paramount research direction for maintaining and understanding the aquatic ecosystem. The question: "What are the aggregate effects on the ecosystem of the current-use and emerging toxicants?" has been placed on a list of the top 40 environmental concerns [22]

A brilliant review has been published by Rosi-Marshall and Royer [23] in Ecosystem, to study the influence of pharmaceuticals on ecosystem function and the research opportunities to tackle the situation, particularly related with the aquatic ecosystem. The pharmaceutical waste compounds found in trace amounts in the environment and ultimately reaching marine life have attracted the attention of researchers and the public due to some alarming consequences. The toxic effects of some of the pharmaceuticals have been recognized, however, their systemic effect on the aquatic ecosystem is still shrouded in mystery. The purpose of the review [23] is important in understanding the origin, distribution, and bi-networking of pharmaceuticals, along with the methods of detecting, quantifying, and analyzing their influence on ecology, including aquatic ecological functions. Accordingly, research should focus on two major aspects, first, to investigate the existence and the concentration of pharmaceuticals in aquatic systems, and second, to investigate their effect on the growth, mortality, and reproduction of single species at a time to understand better. However, the literature revealed that these approaches are missing from the reports, resulting in less or no knowledge about the effects of pharmaceuticals alone or in combination in the aquatic environment