The disposal of pharmaceuticals and the waste generated from pharmaceutical production has an environmental impact, particularly in waterways. The extent of this varies by geography and in relation to the extent of local regulations and the willingness to comply with these regulations. Environmental concerns foremost relate to the detection of trace levels of pharmaceuticals in drinking water (from stimulants and antibiotics to analgesics and antihistamines; plus, scientific evidence of abnormalities in aquatic organisms, and the contribution that some pharmaceuticals make to the spread of antimicrobial resistance. The consequence of a lack of a coherent global (and often national) framework is a potential risk to public health.
The types of pharmaceutical ingredients commonly recovered from water and land include antibiotic, antidepressant, anti-inflammatory, antidiabetic, antiobesity, and estrogen classes. A study conducted in 2022 looked at 258 rivers across the globe, including the Thames in London and the Amazon in Brazil, and used mass spectrometry to screen for pharmaceutical compounds. The results showed the detection of 61 pharmaceuticals, such as carbamazepine, metformin and caffeine, with pharmaceutical pollution contaminating water on every continent. Higher levels of pharmaceutical residues correlated with higher-income countries due to the wide availability of pharmaceutical medications to the general population. The more harmful ingredients detected (based on concentration) were: Propranolol (a beta-blocker for heart problems such as high blood pressure); sulfamethoxazole (an antibiotic for bacterial infection); ciprofloxacin (an antibiotic for bacterial infection) and loratadine (an antihistamine for allergies).
Each of the recovered pharmaceutical ingredients presents an actual or potential biological hazard. Examples of the biological concerns have been highlighted by the OECD:
- Psychiatric drugs alter fish behaviors, with a particular concern for aquaculture. For
example, when exposed to antidepressants, fish exhibit altered feeding behavior and can become more aggressive.
- Other aquatic organisms are also affected and dozens of pharmaceutical compounds
have been detected in insects, for example. Stream insects are the food of larger
organisms and hence pharmaceutical pollutants can readily enter the food chain.
- Discarded pharmaceutical compounds can cause widespread ecological disruption,
including effects on algal production and microbial respiration. Algae that are affected become far less edible for water fleas and fish, leaving them to starve and alterations to the microbial cycle can result in waterways having reduced levels of oxygen.
- Endocrine disrupting pharmaceuticals can cause reproduction toxicity in fish (examples include hormones, contraceptives, and animal feed additives).
- Certain pharmaceutical chemicals affect agricultural yields.
- Drugs leading to increased risk of breast or prostate cancer in humans (especially
those that affect development, growth, reproduction and behavior).
Collectively these are referred to as ‘environmentally persistent pharmaceutical pollutants’ under the Strategic Approach to International Chemicals Management (SAICM), a global framework operated by the United Nations Environment Program for the management of chemicals and wastes. Given that pharmaceutical product design is to protect active ingredients from attack or degradation once they are within the human body, many ingredients only degrade very slowly and will retain biological activity for a considerable period of time.
How Pharmaceutical Waste Ends Up in the Ecosystem
The primary way that residues from pharmaceutical processes enter the environment is through wastewater discharged from manufacturing facilities. The full extent of this risk factor is hampered by many pharmaceutical companies not disclosing details about their manufacturing activities or the identities of the compounds they use, in order to safeguard their intellectual property. The wider adoption of nanomaterials intended for next-generation personalized medicines complicates this further, given the lack of longer-term biological effects relating to these newer class of medicines.
A second way by which pharmaceutical derived chemicals enter the environment is via unused medications, where the responsibility for disposal rests with a pharmacy or with the consumer. A large proportion of prescription and over-the-counter medicines are not used. Consumers are generally encouraged to return these for pharmacies for disposal, although many end up being flushed down sinks or toilets and enter the water system, or they are simply discarded in general waste and end up in landfill. Pharmaceutical originating landfill leachate pollutes soil and is a source of run-offs into water systems.
For medications returned to pharmacies, these are disposed of in different ways by pharmacies. How this is managed varies across different countries and, in the case of the U.S., between different states. Variations in regulations pose different environmental risks and the extent to which they are complied with presents an additional variable.
A third mechanism for release of active pharmaceutical compounds is through normal human or animal use, where traces of the pharmaceutical remain in urine. Problematically, sewage treatment plants are not equipped to remove many of these chemicals and further research and funding are needed to breakdown chemical traces further.
Reasons for the Regulatory Gap
The regulatory gap and current variations in practice partly relates to the discard of pharmaceutical waste being downplayed or excluded from more mature regulations that have
sought to control chemical waste. Focus on tackling pharmaceutical waste through a regulatory framework is a more recent point of inclusion in the waste management strategies of most countries. This despite pharmaceutical contamination having been reported in fresh and marine water source for many decades.
There are different reasons for contradictory national regulations regarding the safe disposal
of medicines and for rules governing pharmaceutical plant effluent discharges. The political sphere of influence will include lobbying from pharmaceutical companies and differing
ideological approaches to regulations from national governments. There is also contradictory scientific information regarding the level of exposure to humans from thousands of different pharmaceutical ingredients. This is further challenged since pharmaceutical chemicals will undergo different transformations and there will be different transfer processes that will increase or decrease the risk of environmental contamination. Complexity is further increased by the variable of different chemicals that do not normally interact from mixing with each other and the variances of biological reactions contingent on an organism’s stage of life. Understanding the extent of pharmaceutical pollution requires more sophisticated biological analyses, including gathering diverse biological endpoints that span several levels of biological organization and life stages. An example of the type of regulatory reform that would be of value, and based on scientific understanding, would be requirements for improving wastewater treatment by introducing technologies that can inactivate a wider range of pharmaceutical pollutants. Such technologies could include ozonation, nanofiltration and advanced oxidation.
Arguably too much research has been orientated toward whether a pharmaceutical waste-product will kill an organism, rather than understanding how pharmaceuticals disrupt ecosystems. In addition, while many chemicals may be of low toxicity in terms of individual discharges but it is unknown what happens either when drugs bioaccumulate or where the full effects are unknown over a prolonged period of time. Even in cases of low toxicity, different medications affect individuals in different ways and may be allergenic to certain individuals.
Developing a Global Solution
Those calling for an international global standard to manage pharmaceutical waste products
and the correct disposal of unwanted medications call for an ‘ecopharmacovigilance’ or ‘ecopharmacology’ framework to be established to enable effective control and monitoring. In doing so, there are attempts to challenge the regulatory indifference towards pharmaceutical pollution.
Most promising are the efforts under the SAICM program. These are seeking to develop a global set of guidances that will ensure similar approaches across all countries. However, to make this a reality, concerted political will be required for this to be embedded within national legal systems.
Dr. Tim Sandle is a practicing microbiologist and science & technology journalist. The author of 30 books, Tim’s journalism has been published on Digital Journal and Pharmaceutical Microbiology Resources. Tim is a visiting tutor at the University of Manchester, U.K. and University College London.