Entry and occurrence of human pharmaceuticals in the environment
Click to enlargePharmaceutical substances have been reported in the environment in at least 89 countries around the
Pharmaceutical substances have been reported in the environment in at least 89 countries around the world.
Source: djahan / Fotolia.com
Residues of pharmaceuticals contaminate water bodies and soils worldwide. They have also been detected in groundwater and, in some cases, even in drinking water. Human pharmaceuticals enter wastewater primarily through human excretion and then pass through sewage treatment plants into water bodies. Due to increasing pharmaceutical consumption, environmental pollution is expected to rise.
Pharmaceuticals are essential tools in medicine and are omnipresent in our daily lives. Almost everyone takes medication either as needed or on a regular basis. Statistically, pharmaceutical consumption increases significantly over a person’s lifetime. In 2018, the per capita consumption among those covered by statutory health insurance was lowest in the 20 to 24 age group, with an average of 76 defined daily doses (DDD) per year. The highest consumption was recorded in the 85 to 89 age group, with 1742 DDD, which is 23 times higher (1). Due to demographic changes, pharmaceutical consumption is expected to continue to rise. According to a study, an increase of approximately 40 to 70 percent is projected by 2045, depending on the scenario (2).
In Germany, around 2,500 different active substances (3) are available in over 100,000 medicinal products for human use(4), with annual consumption exceeding 35,000 tonnes (3). These products are classified as follows:
34,893 over-the-counter
17,546 pharmacy-only
45,490 prescription-only
2,378 narcotic prescription-only
In 2021, medications were most frequently prescribed for the following conditions (5):
Cardiovascular diseases (33%)
Pain and inflammation (13%)
Nervous system disorders (11%)
Gastrointestinal diseases (7%)
Hormonal regulation (6%)
Diabetes (5%)
The consumption of antibiotics continuously increased from 579 tonnes in 2006 to 682 tonnes in 2019, but has been declining since then, reaching 576 tonnes in 2021 (6).
About half of the human pharmaceuticals are classified by the German Environment Agency as potentially environmentally relevant, meaning that according to the current evaluation criteria of the European Medicines Agency (EMA), they would require a detailed environmental assessment.
The approximately 1,300 human pharmaceutical substances with potential environmental relevance account for an annual consumption of about 10,000 tonnes (3). Substances considered not environmentally relevant include herbal medicines, electrolytes, vitamins, peptides, amino acids, and many naturally occurring substances such as minerals. These groups of substances are generally biodegradable, fully metabolised in the body, or their environmental entry through medicinal products is negligible compared to their natural occurrence. Over 50% of the total consumption is attributed to the active ingredients metformin, ibuprofen, metamizole, acetylsalicylic acid, and paracetamol (3).
Development of consumption of human medicinal products in Germany
1.300 active substances are environmentally relevant
Source: Copyright IQVIA. All rights reserved.
Human pharmaceuticals enter the environment through wastewater
Every day, many tonnes of medicinal products are used. Through natural excretion processes, a large proportion of the active substances enter the wastewater treatment plants unchanged and still effective. Another portion is excreted by humans and animals as metabolites. Most of these substances cannot be completely removed by conventional sewage treatment plants and are therefore released into the environment via effluent discharges.
Pharmaceuticals also enter wastewater when they are washed off after applying medicines to the skin. This can be minimised by wiping the hands with a paper towel after applying the medicine, before washing them with water. The paper towel should be disposed of in household waste to prevent pharmaceutical substances from entering the wastewater. This also applies, for example, to used tissues after using nasal drops or ointments. Another pathway for pharmaceuticals into wastewater is the improper disposal of unused medicines via sinks and toilets.
The application form of a drug also influences the amount of active substances that enter the environment. For example, in the treatment of muscle and joint pain, transdermal patches may result in lower environmental contamination compared to topical pain relief creams or gels. Parenteral application forms (such as infusions and injections) generally offer the best balance between dosage control and environmental impact.
In sewage treatment plants, some of the pharmaceutical substances or their metabolites present in wastewater are broken down by microorganisms and/or retained by adsorption onto sewage sludge. The remaining partis discharged into surface waters with the effluent. In the environment, some of these residues continue to degrade, forming transformation products that are often less or no longer pharmacologically active but may have problematic environmental properties, such as persistence (i.e. remaining in the environment for longer) or the potential to leach into groundwater. Some transformation products can even revert to their active form through environmental processes, such as biotransformation by bacteria (7).
The majority of sewage sludge in Germany (80.2% in 2022) is thermally processed through co-incineration in waste-to-energy plants, where the pharmaceutical substances are destroyed (8). However, as of 2024, sewage sludge is still being used as agricultural fertiliser, leading to the accumulation of pharmaceutical residues in soils. According to the German Federal Statistical Office, approximately 1.67 million tonnes of sewage sludge (dry matter) were generated from public wastewater treatment plants in Germany in 2022. Of this, 13.9% was used as fertiliser in agriculture, and 0.8% was applied in landscaping (8). The Sewage Sludge Ordinance, which came into effect in 2017, restricted the quantity and application areas for sewage sludge, limiting its use to arable land. Application on vegetable and fruit cultivation areas, permanent grassland, and in certain water protection zones is no longer permitted.
One potential solution to remove pharmaceuticals from sewage treatment plant effluents is to upgrade sewage treatment plants with a quarternary treatment. Various methods are available (e.g. activated carbon adsorption, ozonation, or membrane filtration), each varying in effectiveness for different pharmaceutical substances. In October 2022, the European Commission proposed equipping all larger sewage treatment plants with a quarternary treatment. The European Council adopted the revised Urban Wastewater Directive on November 5, 2024, which must be transposed into national law within 30 months. According to the directive, 80% of the costs for the implementation and operation of the quarternary treatment will be borne by manufacturers of pharmaceuticals and cosmetic products (9). While the enhanced retention in sewage treatment plants is expected to reduce pharmaceutical residues in large rivers over the coming years, the quarternary treatment is not a standalone solution, as not all pharmaceuticals can be retained. For example, guanylurea (the main metabolite of metformin) and valsartan are not removed by either the biological third or the adsorptive quarternary treatment. Therefore, it remains both ecologically and economically sensible to implement avoidance measures in medical and pharmaceutical practices. Solely upgrading sewage treatment plants will not suffice to meet the Environmental Quality Standards (EQS) proposed by the EU for certain pharmaceuticals.
Pharmaceutical production wastewater can also contain pharmaceutical substances, according to a study by AOK Baden-Württemberg in collaboration with the Rheinisch-Westfälisches Institut für Wasserforschung (IWW). The study examined 10 production sites in India and Europe, measuring 18 antibiotics and finding high concentrations in the wastewater from 4 sites and in the surrounding water bodies (10).
While effluent from sewage treatment plants is the main pathway for human pharmaceuticals to enter the environment, veterinary medicines primarily enter through fertilisers, which are applied to agricultural land in the form of slurry and manure from treated animals.
In addition to human and veterinary pharmaceuticals, other groups of micropollutants are also released into the environment. Other important categories of these trace substances include pesticides, biocides, polycyclic aromatic hydrocarbons (PAHs), and various other chemicals.
Entry pathways of pharmaceutical residues and their occurrence in the environment
Entry pathways of pharmaceutical residues of human (HAM) and animal (TAM) drugs and their occurrence in the environment
Source: Fraunhofer ISI / scientific design (2024)
Pharmaceuticals can be found everywhere in the environment
The first detection of a pharmaceutical substance in German waters occurred accidentally in the early 1990s. It was clofibric acid, a metabolite of the widely prescribed lipid-lowering drug clofibrate, which was discovered during a search for pesticide residues in Berlin's groundwater (11). Since this "Berlin clofibric acid discovery", the issue of pharmaceuticals in the environment has gained increasing attention from scientists and regulatory authorities. In Germany, pharmaceutical residues are now regularly monitored as part of the federal states' water surveillance programmes. These residues are now ubiquitously detected in surface waters, soils, groundwater, and occasionally even in drinking water.
In 2020, 414 pharmaceutical substances, including their metabolites, were detected—145 more than in 2016 (12). Representatives of all major classes of active substances were found, but the most frequently detected were:
Iodinated X-ray contrast agents
Antiepileptics, particularly carbamazepine
Analgesics/anti-inflammatory drugs, especially diclofenac and ibuprofen
Antibiotics, notably sulfamethoxazole
Lipid-lowering agents
Beta-blockers
Numerous pharmaceutical substances are measured in surface waters at concentrations ranging from 0.1 to 1.0 micrograms per litre (µg/L). Many are found at lower concentrations, while some are detected at significantly higher levels. For several years, the federal states have voluntarily included the measurement of various pharmaceutical residues in their monitoring programmes for rivers and lakes. An analysis from 2021 revealed that a total of 41 different pharmaceutical substances and 12 metabolites from thirteen substance classes were present in concentrations exceeding 0.1 µg/L, based on the Health Guidance Value (GOW) for drinking water (in German), in German surface waters. Particularly high concentrations of human pharmaceuticals are measured in the effluents of sewage treatment plants. As a result, surface waters that receive a large amount of wastewater from municipal sewage treatment plants also contain significant amounts of pharmaceutical residues. Various pharmaceutical substances and their metabolites have also been detected in groundwater and, in isolated cases, in drinking water. Sewage sludge, produced as a by-product of wastewater treatment, can also contain high concentrations of pharmaceutical residues. In Germany, 24 different active substances were detected in sewage sludge by 2020. Overall, the number of pharmaceutical findings in sewage sludge is significantly lower than in surface waters. This is primarily because more complex detection methods are required, and thus, only a limited number of substances have been analysed in sewage sludge so far. Additionally, pharmaceuticals are not included among the parameters that have to be measured under the German Sewage Sludge Ordinance (in German).
The German Environment Agency collects data on pharmaceutical findings in the environment worldwide in its UBA Database "Pharmaceuticals in the Environment". By 2020, investigations of samples from 89 countries worldwide detected 992 pharmaceutical substances and their metabolites above the detection limit in soils, surface waters, and sediments—221 more substances than in 2016. Of these, 37 substances, including diclofenac, were found in surface waters, groundwater, and drinking water in all surveyed countries. In some countries, the concentration of certain pharmaceutical substances in surface waters reached levels where negative effects on aquatic organisms, such as fish, cannot be ruled out (12).
Anzahl der gemessenen Arzneimittelwirkstoffe (AMW) ... in Kläranlagenabläufen (KA) ... Source: UmweltbundesamtDiagramm als PDF
Arzneimittelwirkstoffe in Oberflächengewässern Source: Zusammenstellung des Umweltbundesamtes (UBA) 2023 nach Daten der Bund/Länder Arbeitsgemeinschaft Wasser (LAWA)Diagramm als PDF
Metabolite, Transformationsprodukte und ihre Ausgangswirkstoffe in Oberflächengewässern Source: Zusammenstellung des Umweltbundesamtes (UBA) 2023 nach Daten der Bund/Länder Arbeitsgemeinschaft Wasser (LAWA)Diagramm als PDF
Based on internal analysis by UBA using data from the following source: IQVIA MIDAS® Quarterly volume (kg) sales data for Germany Pharmascope and Germany Hospital; Data period: Calendar Year 2010 - 2022, reflecting estimates of real-world activity. Copyright IQVIA. All rights reserved.
Stan HJ, Heberer T, Linkerhägner M 1994: Vorkommen von Clofibrinsäure im aquatischen System – Führt die therapeutische Anwendung zu einer Belastung von Oberflächen-, Grund- und Trinkwasser? Vom Wasser. 83(1994): 57-58
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