Drugs in the environment: emission of drugs, diagnostic aids and disinfectants into wastewater by hospitals in relation to other sources – a review
Introduction
Several thousands of active ingredients are used for drugs in even more products. For example, about 50,000 drugs were registered in Germany for human use, 2700 of which accounted for 90% of the total consumption and which, in turn, contained about 900 different active substances (Glaeske, 1998; Kümmerer, 2001). In the UK, approximately 3000 active substances are licensed (Ayscough et al., 2000). In hospitals as well as in surgeries a variety of substances besides pharmaceuticals are in use for medical purposes as diagnostics and disinfectants. Besides the active substances, formulation adjuvants and, in some instances, pigments and dyes are also drug components. Disinfectants, in particular, are often highly complex products or mixtures of active substances. After application, many drugs are excreted non-metabolised by the patients and enter into wastewater. After their use and sometimes as residual quantities, diagnostic agents and disinfectants also reach the wastewater. Animal husbandry, i.e., veterinary use or use as growth promoters as well as use in aquaculture also discharges drugs and their metabolites as well as disinfectants into the environment through liquid manure and (waste) water or with storm water run-off from fields after application of manure. The substances may finally enter groundwater via soil after application of liquid manure or sewage sludge as fertilisers.
It is often anticipated that pharmaceuticals are easily (bio)degradable in the environment, since they are transformed to some extent in humans. First findings of drugs in the aquatic environment were reported in the 1970s (Tabak and Brunch, 1970; Norpoth et al., 1973; Garrison et al., 1976). Some investigations showed the existence of drugs in public-owned treatment works' (POTWs) effluents. They have been mainly carried out in the UK in the eighties (e.g., Fielding et al., 1981; Richardson and Bowron, 1985; Aherne et al., 1990). The concentrations measured in surface waters and STP effluents were in the ng/l to μg/l range (Table 1). Substances have been detected in effluents from sewage treatment plants as well as in the aquatic system, e.g., in small creeks and big rivers such as the rivers Rhine, Elbe, Neckar, Danube, Po, and others (Ternes, 1998; Klinger and Brauch, 2000; Zuccato et al., 2001) as well as lakes (e.g., Lake Constance, Swiss lakes) (Poiger et al., 2001), in ground water (Heberer et al., 1995; Scheytt et al., 2000) as well as the North Sea and the Adriatic Sea (Buser and Müller, 1998; Zuccato et al., 2001). Emissions from a landfill containing reminders from pharmaceutical production were also reported (Holm et al., 1995).
The detected compounds include a wide variety such as hormones, lipid regulators, pain killers, antibiotics, anti-cancer drugs and other cytotoxic compounds, anti-epileptics as well as those regulating blood pressure (Ayscough et al., 2000).
Tetracycline is one of the most important antibiotics used in agriculture. It was detected in topsoil (Hamscher et al., 2000) in high concentrations (20 mg/kg soil). This concentration is twice as high as the PEC set as a trigger value by the EU for the need of further investigations. Evidence of a wide variety of different active substances in the aquatic environment as well as in liquid manure (Böhm, 1996; Winckler and Graffe, 2000) and in the soil also shows that the active substances are at least not completely eliminated in sewage treatment or in the environment.
Drugs and disinfectants are applied, in contrast to many other chemical substances, because of their specific biological effect. Drugs used in veterinary medicine and husbandry for therapy as well as for prophylactic use and as growth promoters have been assessed (Montforts, 2001). Up to now there is not sufficient data available on the occurrence, fate and effects of drugs in the environment and the risks for humans and the environment possibly connected with (Römbke et al., 1996; Halling-Sørensen et al., 1998; Stuer-Lauridsen et al., 2000; Kümmerer, 2001). According to present knowledge, for risk assessment most pharmaceuticals can be handled like pesticides. The mode of action should be taken into consideration when assessing effects of pharmaceuticals against organisms with standard tests. Some groups need special attention (Kümmerer, 2001):
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Cytostatic agents and immunosupressive drugs, because of their frequently evident carcinogenic, mutagenic or embryotoxic properties as well as other genotoxic compounds (e.g., some antibiotics).
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Antibiotics and disinfectants, because of their pronounced bacterial toxicity and their potential of fostering resistance.
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Hormones, because of their high efficiency/low effect threshold.
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Chlorophenols, chlorine-releasing reagents such as sodium hypochlorite, dichloroisocyanuric acid and others used as disinfectants and as bleaching agents or diagnostics such as organic iodine-containing X-ray contrast media because they contribute to the adsorbable organic halogen compounds (AOX). These are very often not biodegradable and spread widely in the aquatic environment and/or enter the food web.
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Heavy metals, e.g., as part of disinfectants and preservatives containing mercury, cytostatic agents containing platinum or MRI contrast media containing gadolinium, as they are not degradable and highly toxic in some oxidation states.
For risk assessment as well as for risk management it is necessary to know the different sources of emissions of pharmaceuticals into the environment. For most compounds, data are still lacking related to their emission into the environment by different sources such as households or hospitals. Especially for hospitals, data on a nation-wide scale are scarce. The amounts of substances emitted by hospitals are often neglected when predicted environmental concentration (PEC) is calculated. Furthermore, the use patterns of pharmaceuticals are often quite different from the ones in households, i.e., the prescriptions by practitioners. Some antibiotics are used only in hospitals, others only prescribed by practitioners. Furthermore, use patterns of several compounds may vary within different countries. Vancomycine, for example, is widely used as a first-line antibiotic in the USA. In Europe, it's use is very restricted.
In this paper the emission and environmental impacts of antibiotics and cytotoxics, diagnostics and disinfectants by hospitals are described as important sources of the introduction of these substances into the aquatic environment. According to available data, biodegradation is more the exception than the rule. The release from hospitals is compared with other sources as far as data are available. This knowledge is important for risk assessment as well as for risk management. Data, mainly from German and European hospitals of different size and medical service spectrum, are used for this purpose.
Section snippets
Medicine
In Europe, about 10,000 t of antibiotics are consumed per year (FEDESA, 1997). According to these data, 5000 t are due to veterinary purposes (prophylactic use, therapy approx. 3500 t, growth promoting approx. 1500 t). 5000 t are used in medicine. About 2000 t of antibiotics have been manufactured for different purposes in Germany in the early 1990s.
In 1999, approx. 411 t of antibiotics have been used for human applications, 105 t in hospitals. This accounts for 26% of the total consumption.
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