Drugs in the Environment

Kümmerer, Klaus

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Chemosphere

DOI:
10.1016/S0045-6535(01)00144-8

Publication date:
2001

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Citation for pulished version (APA):

Kümmerer, K. (2001). Drugs in the Environment: Emission of Drugs, Diagnostic Aids and Disinfectants into
Wastewater by Hospitals in Relation to other Sources - A Review. Chemosphere, 45(6-7), 957-969. DOI:
10.1016/S0045-6535(01)00144-8

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 Chemosphere 45 (2001) 957±969
www.elsevier.com/locate/chemosphere

Drugs in the environment: emission of drugs, diagnostic aids

and disinfectants into wastewater by hospitals in relation to
other sources ± a review
Klaus K
ummerer
Institute of Environmental Medicine and Hospital Epidemiology, University Hospital Freiburg,
Hugstetter Strasse 55, 79106 Freiburg, Germany
Received 9 August 2000; received in revised form 3 May 2001; accepted 25 May 2001

Abstract

After administration, pharmaceuticals are excreted by the patients into wastewater. Unused medications are
sometimes disposed of in drains. The drugs enter the aquatic environment and eventually reach drinking water if they
are not biodegraded or eliminated during sewage treatment. Additionally, antibiotics and disinfectants are supposed to
disturb the wastewater treatment process and the microbial ecology in surface waters. Furthermore, resistant bacteria
may be selected in the aeration tanks of STPs by the antibiotic substances present. Recently, pharmaceuticals have been
detected in surface water, ground water and drinking water. However, only little is known about the signi®cance of
emissions from households and hospitals. A brief summary of input by di€erent sources, occurrence, and elimination of
di€erent pharmaceutical groups such as antibiotics, anti-tumour drugs, anaesthetics and contrast media as well as AOX
resulting from hospital e‚uent input into sewage water and surface water will be presented. Ó 2001 Elsevier Science
Ltd. All rights reserved.

Keywords: Pharmaceutical; Drug; Hospital e‚uent; Antibiotic; Cytotoxic; Antineoplastic; Diagnostic agent; Disinfectant; Anaesthetic;
AOX; Gadolinium; Platinum

1. Introduction (Ayscough et al., 2000). In hospitals as well as in sur-

1.1. Use
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 di€erent active
substances (Glaeske, 1998; K ummerer, 2001). In the
UK, approximately 3000 active substances are licensed
E-mail address: k.kuemmerer@iuk3.ukl.uni-freiburg.de (K.
K
ummerer).
geries a variety of substances besides pharmaceuticals
are in use for medical purposes as diagnostics and dis-
infectants. 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 waste-
water. After their use and sometimes as residual quan-
tities, 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 ma-
nure and (waste) water or with storm water run-o€ from

0045-6535/01/$ - see front matter Ó 2001 Elsevier Science Ltd. All rights reserved.
PII: S 0 0 4 5 - 6 5 3 5 ( 0 1 ) 0 0 1 4 4 - 8
958 K. Kummerer / Chemosphere 45 (2001) 957±969

®elds after application of manure. The substances may
®nally enter groundwater via soil after application of
liquid manure or sewage sludge as fertilisers.
1.2. Occurrence in the environment and risk
It is often anticipated that pharmaceuticals are easily
(bio)degradable in the environment, since they are
transformed to some extent in humans. First ®ndings 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) e‚uents. 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 ef-
¯uents were in the ng/l to lg/l range (Table 1). Sub-
stances have been detected in e‚uents 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 M uller, 1998; Zuccato et al., 2001).
Emissions from a land®ll 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 di€erent active substances
in the aquatic environment as well as in liquid manure
(Bohm, 1996; Winckler and Grafe, 2000) and in the soil
also shows that the active substances are at least not

Table 1
Detection of pharmaceuticals in the aquatic environment
Active substance group Wastewater Surface water Groundwater (GW), Authors
Drinking water (DW)
Analgesics/ 2.4 Up to 0.5 UBA (1997)
antirheumatic agents
20 Up to 0.5 0.006 (DW) Ternes (1998)
Up to 0.5 Heberer and Stan (1997)
Antibiotics Up to 1.7 Hirsch et al. (1998)
Up to 6a
Approx. 1 UBA (1997)
0.1±1.7 Ternes (1998)
Up to 1 Up to 1 Richardson and Bowron
(1985)
Lipid lowering agents 0.17 (DW) Stan and Linkerhagner
(1992)
1.7 0.55 Ternes (1998)
7.5 (GW) Heberer and Stan (1996)
Up to 1 Heberer and Stan (1997)
0.07 (DW) Stumpf et al. (1996)
Psychopharmacological <1 UBA (1997)
agents
Up to 6.1 Ternes (1998)
Cytostatic agents Up to 0.02 Aherne et al. (1990)
Upto 5 Up to 4a Kummerer et al. (1997a),
Kummerer (1998),
Steger-Hartmann et al.
(1996)
X-ray contrast media 9a Steger-Hartmann et al.
(1998)
10±100a Hirsch et al. (2000)
a
E‚uent from sewage treatment plants.
 K. Kummerer / Chemosphere 45 (2001) 957±969
completely eliminated in sewage treatment or in the
environment.
Drugs and disinfectants are applied, in contrast to
many other chemical substances, because of their spe-
ci®c biological e€ect. 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 sucient data
available on the occurrence, fate and e€ects of drugs in
the environment and the risks for humans and the en-
vironment possibly connected with (R ombke et al.,
1996; Halling-Sùrensen et al., 1998; Stuer-Lauridsen
et al., 2000; K ummerer, 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 e€ects
of pharmaceuticals against organisms with standard
tests. Some groups need special attention (K ummerer,
2001):
· Cytostatic agents and immunosupressive drugs, be-
cause of their frequently evident carcinogenic, muta-
genic or embryotoxic properties as well as other
genotoxic compounds (e.g., some antibiotics).
· Antibiotics and disinfectants, because of their pro-
nounced bacterial toxicity and their potential of fos-
tering resistance.
· Hormones, because of their high eciency/low e€ect
threshold.
· 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 ad-
sorbable organic halogen compounds (AOX). These
are very often not biodegradable and spread widely
in the aquatic environment and/or enter the food
web.
· Heavy metals, e.g., as part of disinfectants and pre-
servatives containing mercury, cytostatic agents con-
taining platinum or MRI contrast media containing
gadolinium, as they are not degradable and highly
toxic in some oxidation states.
Other groups of drugs, for instance analgesics or seda-
tives, are also of interest. Barbiturates were reported to
in¯uence DDT-metabolism in ®sh. They also may mod-
ulate behaviour and predator±prey relations by lowering
swimming velocity and in¯uencing reaction times.
1.3. Sources of pharmaceuticals in the aquatic environ-
ment
For risk assessment as well as for risk management it
is necessary to know the di€erent sources of emissions of
pharmaceuticals into the environment. For most com-
pounds, data are still lacking related to their emission
into the environment by di€erent sources such as
959
households or hospitals. Especially for hospitals, data
on a nation-wide scale are scarce. The amounts of sub-
stances emitted by hospitals are often neglected when
predicted environmental concentration (PEC) is calcu-
lated. Furthermore, the use patterns of pharmaceuticals
are often quite di€erent 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 di€erent countries. Vanc-
omycine, for example, is widely used as a ®rst-line an-
tibiotic 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 disinfec-
tants by hospitals are described as important sources of
the introduction of these substances into the aquatic
environment. According to available data, biodegrada-
tion 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 di€erent size
and medical service spectrum, are used for this purpose.
2. Emissions by hospitals
2.1. Antibiotics
2.1.1. Medicine
In Europe, about 10,000 t of antibiotics are con-
sumed 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 di€erent pur-
poses 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. Between 1994 and
1998, the total consumption increased by about 50 t.
Considering the excretion rates, this would mean that
the entire discharge volume of antibiotic agents into the
wastewater is about 86 t from hospitals. The predicted
concentrations of antibiotics in hospital e‚uents are in
the range of the semi-maximum inhibitory concentration
(MIC50 ) of sensitive pathogenic bacteria for some active
substances and especially for groups of active substances
(0.1±2.9 mg/l). The development of resistance in bio-
logical ®lms (i.e., in areas of high bacterial density), e.g.,
of sewage pipes or in activated sludge can therefore not
be excluded. Concentrations measured for b-lactams in
hospital e‚uents were 20±80 lg/l in hospital e‚uent
during a day course (Cerovec, 2000). Hartmann and co-
workers measured 2±83 lg/l of cipro¯oxacin in the ef-
¯uent of a large Swiss hospital (Hartmann et al., 1998).
960 K. Kummerer / Chemosphere 45 (2001) 957±969
The amounts of antibiotics emitted in total correspond
to a mean antibiotics concentration in municipal
wastewater approaching 50 lg/l. The part of active
substance emitted unchanged is di€erent in relation to its
chemical structure. Tetracyclines, for example, are
hardly discharged into the wastewater because of their
high metabolic rate; moreover, they form relatively
stable complexes with calcium ions.
Active substances representative for important
groups of antibiotics such as quinolones, nitroimidaz-
oles or sulphonamides are of low biodegradability (Al-
Ahmad et al., 1999; K ummerer et al., 2000a). Ingerslev
and Halling-Sùrensen (2000) found that sulphonamides
are even worse degraded than the recalcitrant penta-
chlorophenole. The results agree with the low biode-
gradability determined for other antibiotic agents in soil
(Hubener et al., 1992; Marengo et al., 1997; Weerasin-
ghe and Towner, 1997). In tests with laboratory-scale
sewage treatment plants, about 65% of cipro¯oxacin was
eliminated. 78% of this amount could be re-extracted
from the sludge (K ummerer et al., 2000c) indicating only
bad biodegradation. Cipro¯oxacin was eliminated by
adsorption onto sediment in a test vessel (Bayer, 1991).
For other compounds, adsorption to sewage sludge was
reported (M oehle et al., 1999). Due to adsorption in
activated sludge, it cannot be excluded that resistance
and disturbance of the biological treatment processes
can occur as well as of the sludge reconditioning, in soil
or in sediments. In higher concentrations in test systems,
e€ects against environmental bacteria have been ob-
served (Wiethan et al., 2000). Fluoroquinolon carbonic
acids are photolysed in aqueous solutions under envi-
ronmental conditions (Burhenne et al., 1997a,b). This
path of elimination is of no signi®cance for ingredients
of e‚uents from hospitals on the way to and in the
wastewater treatment facility. Turbidity, water shading,
and water depth, as well as the seasonal changes in
sunlight exposure have a substantial impact on compo-
unds in surface waters. Also, these substances may be
sorbed by sediments and hence be no longer amenable to
photochemical degradation (K ummerer et al., 2001).
Some b-lactams may hydrolyse until they reach the STP
and surface water. Half-lives up to 200 days have been
reported for some b-lactams (Christensen, 1998); for
other b-lactams, half-lives of some days were found in
test systems. Other antibiotics such as tetracyclines or
quinolones have half-lives up to several hundred days in
aquatic environments (Holten-L utzhùft, 2000). After
emission into the aquatic environment, compounds ex-
creted as glucuronides can be cleaved by bacteria,
gaining the unmetabolised compound (M oehle et al.,
1999).
Reduction of used amounts by 50% seems to be
possible for use in medicine by proper use as well as for
farming-related applications (Harrison and Lederberg,
1998).
2.1.2. Veterinary medicine and husbandry
Antibiotics are also used in farming and in aquacul-
ture for prevention, for therapy and as antimicrobially
active substances to improve nutrient uptake in the
gastrointestinal tract (growth promoters). Consumption
in prevention and therapy is largely determined by
modern animal breeding and fattening methods and
conditions. In veterinary use, in total, 5000 t are used in
Europe (FEDESA, 1997). Tetracyclins are by far the
most important group for therapy and prophylaxis
(FEDESA, 1997). Among the four growth promoters
licensed in the EU, monensin and tylosin are the most
important. Most of the compounds were used for pig
and poultry fattening. Only a few percent of the total
quantity is used for other species (cattle, calves, geese,
etc.) (Winckler and Grafe, 2000). Tylosin is not au-
thorised any more in the EU. Based on the data pre-
sented by Winckler and Grafe using total number of
animals from the federal statistical agency (Statistisches
Bundesamt), a total consumption of approx. 900 t can
be estimated for Germany per year. Approximately 50%
of the used amount is due to consumption as growth
promoters. These ®gures are only rough estimations due
to the lack of nationwide data. It was reported only
recently by the Union of Concerned Scientists (2001)
that more than 70% of veterinary antibiotics consump-
tion in the USA is as growth promoters. Up to now it is
unknown which part of the used amount will end up in
surface water by run-o€ from farmland after application
of manure as fertiliser or in ground water after passage
of the soil. Antibiotic agents are also used in aquaculture
(®sh farming) and for pets. They end up in sediments
after application in aquaculture. Tetracyclines were not
eliminated during the storage of the manure over a pe-
riod of 120 days (Winckler and Gra€e, 2000). Strong
reduction of the use of growth promoters was already
demonstrated in Sweden and Denmark. Developing and
using vaccines is a successful way to use the need for
antibiotics in aquaculture as has been demonstrated in
Norway.
2.2. Cytostatic agents
Cytostatic agents are far below the quantitative rel-
evance of other drugs. Seen from the aspect of potential
impact on the environment, cytotoxics are an important
group of drugs in terms of their risk potential for hu-
mans and the environment. These compounds are only
used in medicine. Carcinogenicity, mutagenicity and
fetotoxic properties are often well demonstrated (Skov
et al., 1990). They are mostly used in hospitals. An in-
creasing amount is prescribed by practitioners for out-
patient treatment. For some important cytotoxics (if-
osfamide and cyclophosphamide, Fig. 1) the amounts
used were estimated to be 200±400 kg/yr in Germany
(Kummerer and Al-Ahmad, 2001). In di€erent hospitals,
 K. Kummerer / Chemosphere 45 (2001) 957±969 961

Fig. 1. Formula of some widely used cytotoxics: 5-¯uorouracil, cyclophosphamid, ifosfamide, cis-platinum and carboplatinum (from
left to right).

up to 5 kg/yr of a single substance were used. Some of lower concentrations, also in municipal wastewater. In
the amount administered in hospitals is excreted at home tests with hospital e‚uents, the IC0 was much lower
into municipal sewage by out-patients. The amounts than 1 mg/l as it was for 5-FU in tap water (>128 mg/l)
used in practical surgeries are not documented (Schwabe (Kummerer and Al-Ahmad, 1997). E€ects against higher
and Pa€rath, 2000). The anticipated annual average aquatic organisms such as ®sh or algae have not been
concentrations nation-wide are a few ng/l in the waste- studied intensively for these compounds up to now.
water and presumably below 1 ng/l in surface waters As the cytostatic substances occur in much higher
(Kummerer and Al-Ahmad, 2001). Expected concen- concentrations in patients' urine, a potential health
trations in hospital e‚uents are 5±50 lg/l in hospital hazard must be assumed for personnel entrusted with
e‚uents for single compounds. Concentrations mea- collecting the excretions of patients treated with cyto-
sured during a 24-h course di€ered between a few ng/l statics (Eitel et al., 2000). At the present state of
and the lg/l range within a week indicating a high knowledge, this risk is much higher than for the general
variability of the emissions. population possibly ingesting these substances with
It was shown that biodegradability of cytostatics is drinking water. For this reason, collecting patients'
largely independent from the mode of action and the excretions is not recommended (K ummerer and Al-
chemical structure. Most of the active substances Ahmad, 2001).
investigated proved to have a low biodegradability.
Out of 20 compounds only two met the criteria for
2.3. Anaesthetics
inherent biodegradability (e.g., K ummerer et al., 1996;
Al-Ahmad et al., 1997; K ummerer and Al-Ahmad,
For inhalative anaesthesia, organic ¯ouro(chloro)
1997; Steger-Hartmann et al., 1997; Al-Ahmad and
compounds are used. They are emitted into the atmo-
Kummerer, 2001; K ummerer et al., 2000b,c). There-
sphere. They possess di€erent ozone depletion potentials
fore, the active substances are expected to pass un-
and global warming potentials (Langbein et al., 1999).
changed through municipal sewage treatment plants
For total invasive anaesthesia, amongst others, alkyl-
and thus reach surface waters (K ummerer et al., 1997b;
phenol compounds are used. They are excreted into
Steger-Hartmann et al., 1997; K ummerer and Al-Ah-
wastewater. The most important compound is propofol.
mad, 2001) as far as they are not eliminated by ad-
Up to 10% is metabolised within a few hours to 2,6-
sorption onto sewage sludge. To judge from the results,
diisopropyl-1,4-quinol (Fig. 2); (Guitton et al., 1997).
an elimination of the substances by adsorption (e.g., in
The rate of the excretion of the unchanged drug is about
activated sludge) may be expected only in a small
90%. Data for the total amounts used are not available.
number of compounds such as mitoxantron and epiru-
Both the metabolite and the mother compound are
bicin (K ummerer and Al-Ahmad, 1999). The elimina-
supposed to be biodegradable in sewage treatment
tion of ifosfamide in a sanitary land®ll was investigated
plants. Data are not available, but it is known that
with a laboratory lysimeter. Up to 50% of the ifosfamide
simple phenols are well biodegraded in the environment.
dissolved in the percolation water was eliminated under
methanogenic conditions after 120 days (Schecker et al.,
1998).
Due to their e€ective threshold in relation to bacteria,
an impairment of the self-cleaning capacity of water or
of the biological wastewater puri®cation by cytostatic
agents is not to be expected. Synergistic toxic e€ects of 5-
¯uorouracil with b-lactam antibiotics, cephalosporines,
nor¯oxacin and other antibiotic agents against bacteria
as described in the medical literature also occurred in the
presence of wastewater from hospitals. This is due to
antibiotic agents present in hospital e‚uents and, in Fig. 2. Metabolisation of propofol.
962 K. Kummerer / Chemosphere 45 (2001) 957±969
Fig. 3. Formula of two important quaternary ammonia compounds (QAC) used as disinfectants.
However, the role of the two isopropyl groups in the
ortho position of the hydroxy group is open to question.
2.4. Disinfectants
Large quantities of disinfectants are used in hospitals
for surface, instrument and skin disinfecting, in glue and
size production and use, in food processing and others.
If used for surface disinfecting, product ingredients al-
most inevitably reach the wastewaters. Alcohols and
aldehydes as well as chlorine-containing compounds
such as recalcitrant chlorophenols are used as active
ingredients. Others release chlorine (see Section 2.6) e.g.,
chloramine T which exhibits a lower AOX-forming po-
tential (Hahn et al., 1994). Quaternary ammonium
compounds (QACs) are cationic microbicidal com-
pounds which are important ingredients of widely used
disinfectants for disinfection of surfaces (Russell et al.,
1992). They are one of the most important active in-
gredients besides alcohol and aldehydes. The technical
compound consists of homologues of di€erent alkyl
chain lengths. 12,349 t of QACs were sold in Germany in
1997, 777 t in Belgium, 21,450 t in France and 28,892 t in
the UK (Statistisches Bundesamt, 2000). Detailed data
of the use of QACs in the di€erent sectors are not
available. Concentrations of BzCl up to 6 mg/l have
been measured in hospital e‚uents. 0.05±0.1 mg/l are
expected for QACs in municipal sewage (K ummerer et
al., 1997a). From the concentrations measured in hos-
pital e‚uents and the size of the hospital (in terms of
beds in use), one can calculate that about 10±20 t/yr of
BzCl are used by German hospitals (K ummerer et al.,
1997a). In a large Austrian hospital, about 900 kg/yr had
been used before measures had been taken to reduce
QAC use (K ummerer et al., 1997a,b,c). Data are not
available for the loads of other QACs emitted by the
di€erent sources.
For QACs, contradictory results were reported for
elimination, biodegradability and toxic e€ects against
micro-organisms in STPs as well as in biodegradability
testing (Gerike et al., 1978; ECETOC, 1993; Sanchez-
Leal et al., 1994).
QACs such as BzCl or didecyldimethylammonium
chloride (DDMAC) (Fig. 3) form hydrophobic ion pairs
in the presence of anionic surfactants such as LAS and
SDS. The ion pairing changes the physical and chemical
properties and the surfactant character is masked. The
elimination rates of ion pairs are di€erent from those of
the individual components QAC and anionic surfactant.
Sorption to sludge ¯ocs also depends on other com-
pounds present (Table 2) (K ummerer et al., 2001). The
improved elimination of QACs in the presence of LAS
(Gerike, 1982) is probably not due to a better biode-
gradability of QACs in the presence of LAS, but to the
higher lipophilicity of the ion pair and hence higher
degree of sorption onto the sludge.
The nature of the inorganic counter ion in¯uences the
biodegradability (Janosz-Rajczyk, 1992). The same
results were obtained for organic ions such as the sur-
factants linear alkylbenzenesulfonate (LAS) and sodium
dodecylsulfate (SDS). The biodegradability of the or-
ganic anions was even worse in the presence of the
QACs than the pure compounds (K ummerer et al.,
1998).
QACs are known to be e€ective against aquatic mi-
cro-organisms, even in low concentrations (Tubbing and
Admiraal, 1991). An eciency gap exists in relation to
gram-negative bacteria (Russell et al., 1992). The dose±
e€ect curve of benzalkonium chloride is very steep. An
inhibitory concentration of IC50 ˆ 10 mg/l and
IC100 ˆ 30 mg/l has been found for non-adapted acti-
vated sludge, whereas the ®gure was IC77 ˆ 100 mg/l for
adapted activated sludge (Bayer, 1995). Inhibitory ef-
fects against denitrifying bacteria have been measured
with concentrations as low as 1±2 mg/l (Wagner and
Kayser, 1991). S anchez-Leal et al. (1994) found an EC50
Table 2
Sorption of QACs onto sewage sludge
Compound Adsorption (%)
Blank ±
DEG ±
BzCl 57.8
DDMAC 49.9
BzCl + DEG 31.9
DDMAC + DEG 29.4
BzCl + LAS 64.0
BzCl + LAS + DEG 26.8
DEG: diethylene glycole; BzCl: benzalkonium chloride;
DDMAC: didodecyldimethylammonium chloride; LAS: linear
alkylbenzenesulfonate.
 K. Kummerer / Chemosphere 45 (2001) 957±969
of 0.2±18 mg/l in the Microtoxä test for QACs. They are
likely to disturb the wastewater puri®cation process
(Augustin et al., 1982; Guhl and Gode, 1989). Hingst
and co-workers found elevated prevalence of bacteria
with less sensitivity against BzCl in STP e‚uents (Hingst
et al., 1995). As a consequence of their low biodegra-
dability, the Freiburg University hospital has largely
eliminated products containing benzalkonium chloride
or other QACs for a number of years. Therefore, the
QAC concentration in the e‚uent from this hospital was
much lower than in the ones from hospitals of compa-
rable size and medical service spectrum and even smaller
hospitals (Kummerer et al., 1997b).
Alcohols and aldehydes are easily biodegraded in
STPs. Aldehydes were reported to be present in a con-
centration of 4 mg/l which is supposed to a€ect bacteria
present in the wastewater (Jolibois et al., 2001). Many
others of the active substances such as chlorinated
phenols are of low biodegradability.
2.5. Heavy metals
Concentrations of heavy metals in hospital e‚uents
are comparable to the ones found in municipal sewage
(Gartiser et al., 1994; Leppold, 1997). Concentrations of
platinum, mercury and gadolinium are higher.
2.5.1. Platinum
Platinum can be discharged into various environ-
mental compartments from a variety of sources (Lustig
et al., 1997). Hospital e‚uents contain platinum from
excretions by patients treated with the cytostatic agents
cis-platinum and carboplatinum and others (K ummerer
et al., 1999). Platinum emission from dental surgeries are
only of little importance as platinum is emitted as easily
collectible particles. Because of its high price, most
platinum-containing waters are collected in surgeries
and dental laboratories. The platinum of cytostatic
agents is excreted by the patients and reaches the mu-
nicipal sewer system. The concentrations in 2-h mixed
wastewater samples were between 20 and 3580 ng/l, with
a daily average between <10 and 660 ng/l. Absolute
emissions are lower in hospitals with fewer care services
and of smaller size. The speci®c emissions per bed and
year di€er less than the concentrations, with values be-
tween 14 mg (low medical service spectrum) and 150 mg
per bed and year (maximum medical service spectrum).
Total platinum emissions into the public sewage systems
via hospitals were approx. 14.3 kg/yr in Germany in
1996, which corresponds to 12% of total Pt emissions
from cars and hospitals. 6% and 3.3% were estimated for
the Netherlands and Austria, respectively (K ummerer
et al., 1999). Emissions from other sources such as
electronic devices production, jewellery or glass manu-
factory, cannot be quanti®ed at present (Helmers and
Kummerer, 1999). High concentrations have been found
963
in sewage sludge of cities with a high degree of jewellery
industries (Lottermoser, 1994).
2.5.2. Mercury
In spite of successfully reduced emissions into the
aquatic environment in the past, mercury continues to
be one of the heavy metals whose discharged volume is
still too high. The discharge of mercury from public
health institutions is attributable to preservatives con-
taining mercury usually found in diagnostic agents (e.g.,
Thiomersalâ ) and active ingredients of disinfectants
(Merbromin { ˆ Mercu(ro)chromâ }, Nitromersol) as
well as in diuretic agents such as mercurophyllin (Craig,
1986).
The mercury concentrations measured in the central
wastewater channel of European hospitals of di€erent
sizes were between 0.04 and 2.6 lg/l (Gartiser et al.,
1994; Leppold, 1997), corresponding to an annual load
of approx. 220±250 g for big hospitals. As far as the skin
disinfectant Mercu(ro)chromâ was concerned, it was
shown that the administration of this agent at the
Freiburg University Clinical Centre alone accounted for
about 1±1.5% of the sludge contamination at the sewage
treatment facility in 1996. Based on the volume of pre-
scriptions collected by the national health insurance in-
stitutions in 1994, approximately 100 kg of mercury
were used through Mercu(ro)chromâ in Germany, most
of which is likely to have reached the wastewater during
or after its application. Mercu(ro)chromâ was eventu-
ally replaced by mercury-free alternatives at the Frei-
burg University Clinical Centre (K ummerer, 1998).
Other sources can be broken thermometers. Using
electronic thermometers instead will help to improve the
safety for the personnel as well as to reduce mercury
emissions.
Oxidising components of cleaning or disinfecting
agents help to remobilise mercury in amalgam separa-
tors of dental treatment units (K ummerer et al., 1997c).
The remobilisation of mercury in amalgam separators
with oxidising disinfecting components is expected to
cause an additional mercury load of about 32.5 kg/yr in
Germany. This appears to be little when compared with
other sources and the quantities actually retained by
mercury separators. The International Commission for
the Protection of the River Rhine (IKSR) states in its
interim report that the mercury concentration in surface
water is still two to four times the value of the target
speci®cation. About 44% (of a total of 1.100 kg/a) of the
point-to-point emissions originate from municipal
wastewater (approx. 440 kg/a) (IKSR, 1994). The report
expressly notes that further measures for reducing dis-
charges from the municipal/public sector must be taken
at the source, i.e., at the inlet site. The mercury load
remobilised from dental amalgam through oxidising
disinfecting components in amalgam separators ac-
counts for an average of 7.3% of the public wastewater,
964 K. Kummerer / Chemosphere 45 (2001) 957±969
Fig. 4. Formula of diagnostics. Left: iodine-containing X-ray contrast media (R ˆ NHR0 , OONR00 R000 ; COOH in case of ionic contrast
media); right: (DTPA)Gd-dimeglumine: Diethylenetriaminepentaacetate-Gd(III)-bis-(D -())-1-methylamino-1-desoxy-D -glucite).
which could be lowered to 0.3% if disinfectants without
oxidising properties were used (K ummerer et al., 1997c).
Part of the mercury emitted into the wastewater is also
discharged together with the sludge; the proportion is
unknown. From the medical point of view, the regular
disinfecting of suction units of dental treatment units is
unnecessary, although this is still done in many hospitals
and private dental surgeries. Replacing disinfectants
containing oxidising agents with disinfectants or clean-
ing agents without oxidising components could help to
reduce the mercury emission into the aquatic environ-
ment to a substantial degree. In view of the signi®cance
of mercury in terms of environmental hygiene and the
high toxicity of methyl mercury, biotically formed
mainly in sediments or through di€erent bacteria (Craig,
1986), this measure is reasonable and highly ecient in
terms of the e€orts involved.
2.5.3. The rare earth elements (REE) gadolinium, indium
and osmium
Besides its application in medicine, gadolinium is also
used in nuclear engineering and, together with other
REE, in the production of colour screens. Due to its
high magnetic moment, gadolinium is used in magnetic
resonance imaging (MRI) in the form of organic com-
plexes (Hammond, 1995). Gadolinium complexes typi-
cally used in MRI are gadodiamid and gadopentat (Fig.
4). The Gd-pentate complexes have also been used for
tracer experiments in hydrology (Gutierrez et al., 1997).
Since only recently, the analogue complexes of indium
are in use for MRI. Following administration, the or-
ganic complexes are very quickly excreted unchanged
(>95% within 24 h; Nycomed, 1994). The gadolinium
complexes are emitted into public sewage systems and
into surface waters via the hospital wastewater. The
concentrations measured in hospital e‚uents are in the
range of a few lg/l to 100 lg/l (Kummerer and Helmers,
2000). The natural background concentration of gado-
linium in rivers is about 0.001 lg/l, peak concentrations
of as much as 1.1 g/l in the e‚uent from STPs have been
measured (Bau and Dulski, 1996). Increased concen-
trations have been found in rivers in regions with high
population density for Gd and also for In (Nozaki et al.,
2000). Concentrations of Gd of 0.2 lg/l have been
measured in rivers in¯uenced by STPs discharge (Bau
and Dulski, 1996). With 0.12±0.3 lg/l, the estimated
average gadolinium concentration due to the emission of
contrast media into surface waters in Germany is within
this range, which suggests that the concentrations well
above the natural background are in part due to the
emission of contrast media containing gadolinium
(Kummerer and Helmers, 2000).
Falter and Wilken (1998) have measured between 0.3
and 1.9 mg/kg in waterworks sludges. Vivian (1986)
found 0.6±2 mg/kg in sewage sludges; in own measure-
ments 1.3‹0.05 mg/kg (n ˆ 4) of dry substance were
found. From the good correspondence of these data it
may be assumed that there is no substantial enrichment
in sewage sludge.
The Gd-containing contrast media were shown to be
not biodegradable (Nycomed, 1994). Bau and Dulski
(1996) suspect that the gadolinium complexes are stable
enough to pass through municipal sewage treatment
facilities. With a stability constant of K ˆ 1028 the sta-
bility of Fe(III)±EDTA complexes is very much greater
than those of the appropriate gadolinium complexes
(K ˆ 1023 ) (Falter and Wilken, 1998). However, since
iron(III)salts are used as ¯occulation agents, gadolinium
could be supplanted by Fe(III) from these complexes,
with the e€ect that toxic Gd(III) is released. Gd3‡ is very
toxic to humans when not complexed. GdCl3 may alter
the susceptibility of hepatocytes to toxicity caused by
certain chemicals (Badger et al., 1997) and induce mac-
rophage apoptosis (Mizgerd et al., 1996). The short-term
toxicity of the Gd-containing MRI compounds against
aquatic organisms is low (e.g., EC10 in Ps. putida-growth
inhibition test 870 mg/l; Nycomed, 1994). Bioaccumu-
lation of Gd in carp was investigated by Tu et al. (1994).
Reaction of Gd(DTPA)2 with Zn2‡ and Cu2‡ (25% and
21% in equilibrium, respectively) is reported (Tweedle
and Kumar, 1999). Both ions are present in wastewater.
2.6. AOX and iodised X-ray contrast media
The major mass carriers for the AOX in hospital
e‚uents are most likely iodised X-ray contrast media,
solvents, disinfectants, cleaners and drugs containing
chlorine. Studies conducted at a number of German
 K. Kummerer / Chemosphere 45 (2001) 957±969
hospitals have shown the AOX concentration in mixed
daily samples taken at the discharge points into the
public sewage system is in the range 0.13±0.94 mg/l
(é 0.43 mg/l), but that the AOX contamination in
wastewater part ¯ows from individual sectors of hospi-
tals can be substantially higher (Gartiser et al., 1994). In
24-h mixing samples from European hospitals, AOX
concentrations varied from 1.1±7.76 mg/l (Haiû et al.,
1998). In general, the maximum contribution of drugs to
the AOX is not above 11% (K ummerer et al., 1998).
Beyond that it is also known that the AOX concentra-
tion in the urine of persons not treated with drugs is very
low. It is normally between 0.001 mg/l (Koppe and
Stozek, 1993) and 0.2 mg/l (Schulz and Hahn, 1997).
Due to the dilution e€ect, no substantial contribution
from this source is consequently expected.
Chloramine T and other agents such as sodium hy-
pochlorite or 1,3-dichlorisocyanuric acid form elemen-
tary chlorine which is responsible for the disinfecting
e€ect of these substances. Organic halogen compounds
are formed by reaction of chlorine with organic waste-
water compounds. An additional AOX in the wastewater
will result. According to the literature, the AOX forma-
tion through chloramine T is, however, substantially
lower than through other elementary chlorine formers
such as sodium hypochlorite (Hahn et al., 1994). 4±6% of
the latter generate AOX (Schulz and Hahn, 1997). This
additional AOX pollution can be avoided by dispensing
with chlorine-forming ingredients such as hypochlorite
or 1,3-dichlorisocyanuric acid in cleaners and disinfec-
tants, or in direct chlorine bleach. The disinfecting with
active substances and electro-chemical procedures not
splitting o€ elementary chlorine can also help to reduce
AOX (Schulz and Hahn, 1997). PVP-iodine-based dis-
infectants do not contribute to AOX. Brominated or-
ganic compounds are negligible for the AOX in the
e‚uents from hospitals. However, hospitals cannot be
neglected as contributors to AOX in urban wastewater.
A surprisingly high proportion of AOI in the AOX
was found in municipal wastewater. The organic iodine
compounds may account for about 50% of the AOX as
AOI input into municipal wastewater. Also, unlike the
AOCl, it showed a pronounced weekly progression with
minimal values at weekends. With reference to chloride,
the proportion of AOI ¯uctuated between 23% and 53%
of the total AOX. The proportion of AOI was particu-
larly high when e‚uents from hospitals were discharged
(Jekel and Wischnak, 2000). During the examination of
the distribution of the molecular weight of the water
ingredients detected with organic sum parameters, it was
found that 80% of the organic substances in the AOI
belong to the low molecular fraction (mol. mass below
1000; Jekel and Wischnak, 2000). The molecular weights
of most organic iodine X-ray contrast media are in the
range 700±900. Surveys and comparisons with mea-
surements have demonstrated that a large proportion of
965
the AOX from hospital e‚uents is present as AOI
(Ziegler et al., 1997; Erbe et al., 1998; Haiû et al., 1998).
This may be seen as an indicator that the AOI is mainly
caused by X-ray contrast media. Especially in hospitals
with major radiological departments, iodised X-ray
contrast media make a substantial contribution towards
AOX. They are not easily and completely biodegradable
(Kalsch, 1992) and have been detected even in the Lake
Constance in concentrations up to 10 ng/l (Roûknecht
and Hetzenauer, 2000) as well as in drinking water
(Hirsch et al., 2000). About 360 t of iodised X-ray
contrast media have been used in Germany per year
(Jekel and Wischnak, 2000).
The AOI is not necessarily the greatest contributor to
the AOX in the e‚uents from hospitals, instead, organic
iodine compounds can account for about 50% of the
AOX pollution (Haiû et al., 1998). Since iodised X-ray
contrast media are not only used in hospitals but also in
practical surgeries, a substantial proportion of iodine in
the public sewage system could be di€usely discharged
through X-ray contrast media. Particularly when inex-
plicably high AOX values are measured, this could be an
indication of a hospital with a radiological department,
major radiological surgeries or may be a manufacturer
of X-ray contrast media being the discharger.
Compared with other drugs, a particularly low gen-
eral and local toxicity is speci®ed for contrast media
which are always given in high dosage. Contrast media
are not allowed to have any intrinsic pharmacodynamic
e€ects. This may be seen as an indicator that their dis-
charge into the aquatic environment is less problematic
under the aspect of human toxicity. Therefore, German
authorities have agreed not to count AOI for the total
AOX. This is seen under aspects of drinking water hy-
giene and possible long-term e€ects (e.g., products of
photodegradation) not a sustainable approach. Due to
their persistence and high solubility in water, contrast
media will spread widely in the aquatic environment.
Therefore, they ought to be discharged in the smallest
quantities possible. The issue of how to assess contrast
media with their high persistence and mobility in water
in terms of ecotoxicology and environmental hygiene, as
well as measures to reduce their environmental burden
need to be investigated further.
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